Review and update of mutations causing Waardenburg syndrome.

PubMed

Pingault, Véronique; Ente, Dorothée; Dastot-Le Moal, Florence; Goossens, Michel; Marlin, Sandrine; Bondurand, Nadège

2010-04-01

Waardenburg syndrome (WS) is characterized by the association of pigmentation abnormalities, including depigmented patches of the skin and hair, vivid blue eyes or heterochromia irides, and sensorineural hearing loss. However, other features such as dystopia canthorum, musculoskeletal abnormalities of the limbs, Hirschsprung disease, or neurological defects are found in subsets of patients and used for the clinical classification of WS. Six genes are involved in this syndrome: PAX3 (encoding the paired box 3 transcription factor), MITF (microphthalmia-associated transcription factor), EDN3 (endothelin 3), EDNRB (endothelin receptor type B), SOX10 (encoding the Sry bOX10 transcription factor), and SNAI2 (snail homolog 2), with different frequencies. In this review we provide an update on all WS genes and set up mutation databases, summarize molecular and functional data available for each of them, and discuss the applications in diagnostics and genetic counseling. (c) 2010 Wiley-Liss, Inc.

Functional analysis of a SOX10 gene mutation associated with Waardenburg syndrome II.

PubMed

Wang, Xue-Ping; Hao, Zi-Qi; Liu, Ya-Lan; Mei, Ling-Yun; He, Chu-Feng; Niu, Zhi-Jie; Sun, Jie; Zhao, Yu-Lin; Feng, Yong

2017-11-04

Waardenburg syndrome (WS) is an autosomal dominant inherited non-syndromic type of hereditary hearing loss characterized by varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four subtypes (WS1-WS4) based on additional symptoms. WS2 is characterized by the absence of additional symptoms. Recently, we identified a SOX10 missense mutation c.422T > C (p.L141P) associated with WS2. We performed functional assays and found the mutant loses DNA-binding capacity, shows aberrant cytoplasmic and nuclear localization, and fails to interact with PAX3. Therefore, the mutant cannot transactivate the MITF promoter effectively, inhibiting melanin synthesis and leading to WS2. Our study confirmed haploinsufficiency as the underlying pathogenesis for WS2. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural tube defects in Waardenburg syndrome: A case report and review of the literature.

PubMed

Hart, Joseph; Miriyala, Kalpana

2017-09-01

Waardenburg syndrome type 1 (WS1) is an autosomal dominant genetic condition characterized by sensorineural deafness and pigment abnormalities, and is caused by variants in the PAX3 homeodomain. PAX3 variants have been associated with severe neural tube defects in mice and humans, but the frequency and clinical manifestations of this symptom remain largely unexplored in humans. Consequently, the role of PAX3 in human neural tube formation remains a study of interest, for clinical as well as research purposes. Though the association between spina bifida and WS1 is now well-documented, no study has attempted to characterize the range of spina bifida phenotypes seen in WS. Spina bifida encompasses several diagnoses with a wide scope of clinical severity, ranging from spina bifida occulta to myelomeningocele. We present a patient with Waardenburg syndrome type 1 caused by a novel missense variant in PAX3, presenting with myelomeningocele, Arnold-Chiari malformation, and hydrocephalus at birth. Additionally, we review 32 total cases of neural tube defects associated with WS. Including this report, there have been 15 published cases of myelomeningocele, 10 cases of unspecified spina bifida, 3 cases of sacral dimples, 0 cases of meningocele, and 4 cases of miscellaneous other neural tube defects. Though the true frequency of each phenotype cannot be determined from this collection of cases, these results demonstrate that Waardenburg syndrome type 1 carries a notable risk of severe neural tube defects, which has implications in prenatal and genetic counseling. © 2017 Wiley Periodicals, Inc.

Alu-mediated deletion of SOX10 regulatory elements in Waardenburg syndrome type 4

PubMed Central

Bondurand, Nadége; Fouquet, Virginie; Baral, Viviane; Lecerf, Laure; Loundon, Natalie; Goossens, Michel; Duriez, Benedicte; Labrune, Philippe; Pingault, Veronique

2012-01-01

Waardenburg syndrome type 4 (WS4) is a rare neural crest disorder defined by the combination of Waardenburg syndrome (sensorineural hearing loss and pigmentation defects) and Hirschsprung disease (intestinal aganglionosis). Three genes are known to be involved in this syndrome, that is, EDN3 (endothelin-3), EDNRB (endothelin receptor type B), and SOX10. However, 15–35% of WS4 remains unexplained at the molecular level, suggesting that other genes could be involved and/or that mutations within known genes may have escaped previous screenings. Here, we searched for deletions within recently identified SOX10 regulatory sequences and describe the first characterization of a WS4 patient presenting with a large deletion encompassing three of these enhancers. Analysis of the breakpoint region suggests a complex rearrangement involving three Alu sequences that could be mediated by a FosTes/MMBIR replication mechanism. Taken together with recent reports, our results demonstrate that the disruption of highly conserved non-coding elements located within or at a long distance from the coding sequences of key genes can result in several neurocristopathies. This opens up new routes to the molecular dissection of neural crest disorders. PMID:22378281

Alu-mediated deletion of SOX10 regulatory elements in Waardenburg syndrome type 4.

PubMed

Bondurand, Nadége; Fouquet, Virginie; Baral, Viviane; Lecerf, Laure; Loundon, Natalie; Goossens, Michel; Duriez, Benedicte; Labrune, Philippe; Pingault, Veronique

2012-09-01

Waardenburg syndrome type 4 (WS4) is a rare neural crest disorder defined by the combination of Waardenburg syndrome (sensorineural hearing loss and pigmentation defects) and Hirschsprung disease (intestinal aganglionosis). Three genes are known to be involved in this syndrome, that is, EDN3 (endothelin-3), EDNRB (endothelin receptor type B), and SOX10. However, 15-35% of WS4 remains unexplained at the molecular level, suggesting that other genes could be involved and/or that mutations within known genes may have escaped previous screenings. Here, we searched for deletions within recently identified SOX10 regulatory sequences and describe the first characterization of a WS4 patient presenting with a large deletion encompassing three of these enhancers. Analysis of the breakpoint region suggests a complex rearrangement involving three Alu sequences that could be mediated by a FosTes/MMBIR replication mechanism. Taken together with recent reports, our results demonstrate that the disruption of highly conserved non-coding elements located within or at a long distance from the coding sequences of key genes can result in several neurocristopathies. This opens up new routes to the molecular dissection of neural crest disorders.

A novel PAX3 mutation in a Japanese boy with Waardenburg syndrome type 1.

PubMed

Yoshida, Yu; Doi, Rieko; Adachi, Kaori; Nanba, Eiji; Kodani, Isamu; Ryoke, Kazuo

2016-01-01

Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant disorder characterized by hair hypopigmentation, abnormal iris pigmentation, and congenital hearing loss. WS1 is caused by mutations in paired box gene 3 (PAX3). We identified a novel PAX3 mutation (c.1107 C>G, p.Ser369Arg) in a Japanese WS1 patient showing abnormal right iris pigmentation, right-sided congenital hearing loss, synophrys, incomplete left cleft lip, and cryptorchidism.

Loading of PAX3 to Mitotic Chromosomes Is Mediated by Arginine Methylation and Associated with Waardenburg Syndrome*

PubMed Central

Wu, Tsu-Fang; Yao, Ya-Li; Lai, I-Lu; Lai, Chien-Chen; Lin, Pei-Lun; Yang, Wen-Ming

2015-01-01

PAX3 is a transcription factor critical to gene regulation in mammalian development. Mutations in PAX3 are associated with Waardenburg syndrome (WS), but the mechanism of how mutant PAX3 proteins cause WS remains unclear. Here, we found that PAX3 loads on mitotic chromosomes using its homeodomain. PAX3 WS mutants with mutations in homeodomain lose the ability to bind mitotic chromosomes. Moreover, loading of PAX3 on mitotic chromosomes requires arginine methylation, which is regulated by methyltransferase PRMT5 and demethylase JMJD6. Mutant PAX3 proteins that lose mitotic chromosome localization block cell proliferation and normal development of zebrafish. These results reveal the molecular mechanism of PAX3s loading on mitotic chromosomes and the importance of this localization pattern in normal development. Our findings suggest that PAX3 WS mutants interfere with the normal functions of PAX3 in a dominant negative manner, which is important to the understanding of the pathogenesis of Waardenburg syndrome. PMID:26149688

A PAX3 polymorphism (T315K) in a family exhibiting Waardenburg Syndrome type 2.

PubMed

Wang, C; Kim, E; Attaie, A; Smith, T N; Wilcox, E R; Lalwani, A K

1998-02-01

Waardenburg Syndrome (WS) is an autosomal-dominant disorder phenotypically characterized by sensorineural hearing loss and pigmentary disturbances. Presence of dystopia canthorum is indicative of WS type 1 and results from defects in the PAX3 gene, whereas normally located medial canthi is characteristic of type 2 WS (WS2) and is associated with defects in the microphthalmia-associated transcription factor (MIFT) gene. Here a neutral polymorphism is reported in the PAX3 gene (T315K) in a family with WS2. Copyright 1998 Academic Press Limited

A de novo deletion mutation in SOX10 in a Chinese family with Waardenburg syndrome type 4.

PubMed

Wang, Xiong; Zhu, Yaowu; Shen, Na; Peng, Jing; Wang, Chunyu; Liu, Haiyi; Lu, Yanjun

2017-01-27

Waardenburg syndrome type 4 (WS4) or Waardenburg-Shah syndrome is a rare genetic disorder with a prevalence of <1/1,000,000 and characterized by the association of congenital sensorineural hearing loss, pigmentary abnormalities, and intestinal aganglionosis. There are three types of WS4 (WS4A-C) caused by mutations in endothelin receptor type B, endothelin 3, and SRY-box 10 (SOX10), respectively. This study investigated a genetic mutation in a Chinese family with one WS4 patient in order to improve genetic counselling. Genomic DNA was extracted, and mutation analysis of the three WS4 related genes was performed using Sanger sequencing. We detected a de novo heterozygous deletion mutation [c.1333delT (p.Ser445Glnfs*57)] in SOX10 in the patient; however, this mutation was absent in the unaffected parents and 40 ethnicity matched healthy controls. Subsequent phylogenetic analysis and three-dimensional modelling of the SOX10 protein confirmed that the c.1333delT heterozygous mutation was pathogenic, indicating that this mutation might constitute a candidate disease-causing mutation.

A de novo deletion mutation in SOX10 in a Chinese family with Waardenburg syndrome type 4

PubMed Central

Wang, Xiong; Zhu, Yaowu; Shen, Na; Peng, Jing; Wang, Chunyu; Liu, Haiyi; Lu, Yanjun

2017-01-01

Waardenburg syndrome type 4 (WS4) or Waardenburg-Shah syndrome is a rare genetic disorder with a prevalence of <1/1,000,000 and characterized by the association of congenital sensorineural hearing loss, pigmentary abnormalities, and intestinal aganglionosis. There are three types of WS4 (WS4A–C) caused by mutations in endothelin receptor type B, endothelin 3, and SRY-box 10 (SOX10), respectively. This study investigated a genetic mutation in a Chinese family with one WS4 patient in order to improve genetic counselling. Genomic DNA was extracted, and mutation analysis of the three WS4 related genes was performed using Sanger sequencing. We detected a de novo heterozygous deletion mutation [c.1333delT (p.Ser445Glnfs*57)] in SOX10 in the patient; however, this mutation was absent in the unaffected parents and 40 ethnicity matched healthy controls. Subsequent phylogenetic analysis and three-dimensional modelling of the SOX10 protein confirmed that the c.1333delT heterozygous mutation was pathogenic, indicating that this mutation might constitute a candidate disease-causing mutation. PMID:28128317

A novel PAX3 mutation in a Japanese boy with Waardenburg syndrome type 1

PubMed Central

Yoshida, Yu; Doi, Rieko; Adachi, Kaori; Nanba, Eiji; Kodani, Isamu; Ryoke, Kazuo

2016-01-01

Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant disorder characterized by hair hypopigmentation, abnormal iris pigmentation, and congenital hearing loss. WS1 is caused by mutations in paired box gene 3 (PAX3). We identified a novel PAX3 mutation (c.1107 C>G, p.Ser369Arg) in a Japanese WS1 patient showing abnormal right iris pigmentation, right-sided congenital hearing loss, synophrys, incomplete left cleft lip, and cryptorchidism. PMID:27081571

Novel splice mutation in microthalmia-associated transcription factor in Waardenburg Syndrome.

PubMed

Brenner, Laura; Burke, Kelly; Leduc, Charles A; Guha, Saurav; Guo, Jiancheng; Chung, Wendy K

2011-01-01

Waardenburg Syndrome (WS) is a syndromic form of hearing loss associated with mutations in six different genes. We identified a large family with WS that had previously undergone clinical testing, with no reported pathogenic mutation. Using linkage analysis, a region on 3p14.1 with an LOD score of 6.6 was identified. Microthalmia-Associated Transcription Factor, a gene known to cause WS, is located within this region of linkage. Sequencing of Microthalmia-Associated Transcription Factor demonstrated a c.1212 G>A synonymous variant that segregated with the WS in the family and was predicted to cause a novel splicing site that was confirmed with expression analysis of the mRNA. This case illustrates the need to computationally analyze novel synonymous sequence variants for possible effects on splicing to maximize the clinical sensitivity of sequence-based genetic testing.

A novel mutation in PAX3 associated with Waardenburg syndrome type I in a Chinese family.

PubMed

Xiao, Yun; Luo, Jianfen; Zhang, Fengguo; Li, Jianfeng; Han, Yuechen; Zhang, Daogong; Wang, Mingming; Ma, Yalin; Xu, Lei; Bai, Xiaohui; Wang, Haibo

2016-01-01

The novel compound heterozygous mutation in PAX3 was the key genetic reason for WS1 in this family, which was useful to the molecular diagnosis of WS1. Screening the pathogenic mutations in a four generation Chinese family with Waardenburg syndrome type I (WS1). WS1 was diagnosed in a 4-year-old boy according to the Waardenburg syndrome Consortium criteria. The detailed family history revealed four affected members in the family. Routine clinical, audiological examination, and ophthalmologic evaluation were performed on four affected and 10 healthy members in this family. The genetic analysis was conducted, including the targeted next-generation sequencing of 127 known deafness genes combined with Sanger sequencing, TA clone and bioinformatic analysis. A novel compound heterozygous mutation c.[169_170insC;172_174delAAG] (p.His57ProfsX55) was identified in PAX3, which was co-segregated with WS1 in the Chinese family. This mutation was absent in the unaffected family members and 200 ethnicity-matched controls. The phylogenetic analysis and three-dimensional (3D) modeling of Pax3 protein further confirmed that the novel compound heterozygous mutation was pathogenic.

A case report of reversible generalized seizures in a patient with Waardenburg syndrome associated with a novel nonsense mutation in the penultimate exon of SOX10.

PubMed

Suzuki, Noriomi; Mutai, Hideki; Miya, Fuyuki; Tsunoda, Tatsuhiko; Terashima, Hiroshi; Morimoto, Noriko; Matsunaga, Tatsuo

2018-05-23

Waardenburg syndrome type 1 (WS1) can be distinguished from Waardenburg syndrome type 2 (WS2) by the presence of dystopia canthorum. About 96% of WS1 are due to PAX3 mutations, and SOX10 mutations have been reported in 15% of WS2. This report describes a patient with WS1 who harbored a novel SOX10 nonsense mutation (c.652G > T, p.G218*) in exon 3 which is the penultimate exon. The patient had mild prodromal neurological symptoms that were followed by severe attacks of generalized seizures associated with delayed myelination of the brain. The immature myelination recovered later and the neurological symptoms could be improved. This is the first truncating mutation in exon 3 of SOX10 that is associated with neurological symptoms in Waardenburg syndrome. Previous studies reported that the neurological symptoms that associate with WS are congenital and irreversible. These findings suggest that the reversible neurological phenotype may be associated with the nonsense mutation in exon 3 of SOX10. When patients of WS show mild prodromal neurological symptoms, the clinician should be aware of the possibility that severe attacks of generalized seizures may follow, which may be associated with the truncating mutation in exon 3 of SOX10.

Clinical variability of Waardenburg-Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus.

PubMed

Tüysüz, Beyhan; Collin, Anna; Arapoğlu, Müjde; Suyugül, Nezir

2009-10-01

Waardenburg-Shah syndrome (Waardenburg syndrome type IV-WS4) is an auditory-pigmentary disorder that combines clinical features of pigmentary abnormalities of the skin, hair and irides, sensorineural hearing loss, and Hirschsprung disease (HSCR). Mutations in the endothelin-B receptor (EDNRB) gene on 13q22 have been found to cause this syndrome. Mutations in both alleles cause the full phenotype, while heterozygous mutations cause isolated HSCR or HSCR with minor pigmentary anomalies and/or sensorineural deafness. We investigated the status of the EDNRB gene, by FISH analysis, in three patients with de novo proximal 13q deletions detected at cytogenetic analysis and examined the clinical variability of WS4 among these patients. Chromosome 13q was screened with locus specific FISH probes and breakpoints were determined at 13q22.1q31.3 in Patients 1 and 3, and at 13q21.1q31.3 in Patient 2. An EDNRB specific FISH probe was deleted in all three patients. All patients had common facial features seen in proximal 13q deletion syndrome and mild mental retardation. However, findings related to WS4 were variable; Patient 1 had hypopigmentation of the irides and HSCR, Patient 2 had prominent bicolored irides and mild bilateral hearing loss, and Patient 3 had only mild unilateral hearing loss. These data contribute new insights into the pathogenesis of WS4.

Identification and functional analysis of SOX10 missense mutations in different subtypes of Waardenburg syndrome.

PubMed

Chaoui, Asma; Watanabe, Yuli; Touraine, Renaud; Baral, Viviane; Goossens, Michel; Pingault, Veronique; Bondurand, Nadege

2011-12-01

Waardenburg syndrome (WS) is a rare disorder characterized by pigmentation defects and sensorineural deafness, classified into four clinical subtypes, WS1-S4. Whereas the absence of additional features characterizes WS2, association with Hirschsprung disease defines WS4. WS is genetically heterogeneous, with six genes already identified, including SOX10. About 50 heterozygous SOX10 mutations have been described in patients presenting with WS2 or WS4, with or without myelination defects of the peripheral and central nervous system (PCWH, Peripheral demyelinating neuropathy-Central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease, or PCW, PCWH without HD). The majority are truncating mutations that most often remove the main functional domains of the protein. Only three missense mutations have been thus far reported. In the present study, novel SOX10 missense mutations were found in 11 patients and were examined for effects on SOX10 characteristics and functions. The mutations were associated with various phenotypes, ranging from WS2 to PCWH. All tested mutations were found to be deleterious. Some mutants presented with partial cytoplasmic redistribution, some lost their DNA-binding and/or transactivation capabilities on various tissue-specific target genes. Intriguingly, several mutants were redistributed in nuclear foci. Whether this phenomenon is a cause or a consequence of mutation-associated pathogenicity remains to be determined, but this observation could help to identify new SOX10 modes of action. © 2011 Wiley-Liss, Inc.

Loading of PAX3 to Mitotic Chromosomes Is Mediated by Arginine Methylation and Associated with Waardenburg Syndrome.

PubMed

Wu, Tsu-Fang; Yao, Ya-Li; Lai, I-Lu; Lai, Chien-Chen; Lin, Pei-Lun; Yang, Wen-Ming

2015-08-14

PAX3 is a transcription factor critical to gene regulation in mammalian development. Mutations in PAX3 are associated with Waardenburg syndrome (WS), but the mechanism of how mutant PAX3 proteins cause WS remains unclear. Here, we found that PAX3 loads on mitotic chromosomes using its homeodomain. PAX3 WS mutants with mutations in homeodomain lose the ability to bind mitotic chromosomes. Moreover, loading of PAX3 on mitotic chromosomes requires arginine methylation, which is regulated by methyltransferase PRMT5 and demethylase JMJD6. Mutant PAX3 proteins that lose mitotic chromosome localization block cell proliferation and normal development of zebrafish. These results reveal the molecular mechanism of PAX3s loading on mitotic chromosomes and the importance of this localization pattern in normal development. Our findings suggest that PAX3 WS mutants interfere with the normal functions of PAX3 in a dominant negative manner, which is important to the understanding of the pathogenesis of Waardenburg syndrome. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Paediatric Cochlear Implantation in Patients with Waardenburg Syndrome

PubMed Central

van Nierop, Josephine W.I.; Snabel, Rebecca R.; Langereis, Margreet; Pennings, Ronald J.E.; Admiraal, Ronald J.C.; Mylanus, Emmanuel A.M.; Kunst, Henricus P.M.

2016-01-01

Objective To analyse the benefit of cochlear implantation in young deaf children with Waardenburg syndrome (WS) compared to a reference group of young deaf children without additional disabilities. Method A retrospective study was conducted on children with WS who underwent cochlear implantation at the age of 2 years or younger. The post-operative results for speech perception (phonetically balanced standard Dutch consonant-vocal-consonant word lists) and language comprehension (the Reynell Developmental Language Scales, RDLS), expressed as a language quotient (LQ), were compared between the WS group and the reference group by using multiple linear regression analysis. Results A total of 14 children were diagnosed with WS, and 6 of them had additional disabilities. The WS children were implanted at a mean age of 1.6 years and the 48 children of the reference group at a mean age of 1.3 years. The WS children had a mean phoneme score of 80% and a mean LQ of 0.74 at 3 years post-implantation, and these results were comparable to those of the reference group. Only the factor additional disabilities had a significant negative influence on auditory perception and language comprehension. Conclusions Children with WS performed similarly to the reference group in the present study, and these outcomes are in line with the previous literature. Although good counselling about additional disabilities concomitant to the syndrome is relevant, cochlear implantation is a good rehabilitation method for children with WS. PMID:27245679

Paediatric Cochlear Implantation in Patients with Waardenburg Syndrome.

PubMed

van Nierop, Josephine W I; Snabel, Rebecca R; Langereis, Margreet; Pennings, Ronald J E; Admiraal, Ronald J C; Mylanus, Emmanuel A M; Kunst, Henricus P M

2016-01-01

To analyse the benefit of cochlear implantation in young deaf children with Waardenburg syndrome (WS) compared to a reference group of young deaf children without additional disabilities. A retrospective study was conducted on children with WS who underwent cochlear implantation at the age of 2 years or younger. The post-operative results for speech perception (phonetically balanced standard Dutch consonant-vocal-consonant word lists) and language comprehension (the Reynell Developmental Language Scales, RDLS), expressed as a language quotient (LQ), were compared between the WS group and the reference group by using multiple linear regression analysis. A total of 14 children were diagnosed with WS, and 6 of them had additional disabilities. The WS children were implanted at a mean age of 1.6 years and the 48 children of the reference group at a mean age of 1.3 years. The WS children had a mean phoneme score of 80% and a mean LQ of 0.74 at 3 years post-implantation, and these results were comparable to those of the reference group. Only the factor additional disabilities had a significant negative influence on auditory perception and language comprehension. Children with WS performed similarly to the reference group in the present study, and these outcomes are in line with the previous literature. Although good counselling about additional disabilities concomitant to the syndrome is relevant, cochlear implantation is a good rehabilitation method for children with WS. © 2016 S. Karger AG, Basel.

Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes.

PubMed

Farrer, L A; Arnos, K S; Asher, J H; Baldwin, C T; Diehl, S R; Friedman, T B; Greenberg, J; Grundfast, K M; Hoth, C; Lalwani, A K

1994-10-01

Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes, and distinctive facial features. Clinically, WS type I (WS1) is differentiated from WS type II (WS2) by the high frequency of dystopia canthorum in the family. In some families, WS is caused by mutations in the PAX3 gene on chromosome 2q. We have typed microsatellite markers within and flanking PAX3 in 41 WS1 kindreds and 26 WS2 kindreds in order to estimate the proportion of families with probable mutations in PAX3 and to study the relationship between phenotypic and genotypic heterogeneity. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that WS is linked to PAX3 in 60% of all WS families and in 100% of WS1 families. None of the WS2 families were linked. In those families in which equivocal lod scores (between -2 and +1) were found, PAX3 mutations have been identified in 5 of the 15 WS1 families but in none of the 4 WS2 families. Although preliminary studies do not suggest any association between the phenotype and the molecular pathology in 20 families with known PAX3 mutations and in four patients with chromosomal abnormalities in the vicinity of PAX3, the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3.

Cochlear implantation in Waardenburg syndrome: The Indian scenario.

PubMed

Deka, Ramesh Chandra; Sikka, Kapil; Chaturvedy, Gaurav; Singh, Chirom Amit; Venkat Karthikeyan, C; Kumar, Rakesh; Agarwal, Shivani

2010-10-01

Children with Waardenburg syndrome (WS) exhibiting normal inner ear anatomy, like those included in our cohort, derive significant benefit from cochlear implantation and results are comparable to those reported for the general population of implanted children. The patient population of WS accounts for approximately 2% of congenitally deaf children. The purpose of this retrospective case review was to describe the outcomes for those children with WS who have undergone cochlear implantation. On retrospective chart review, there were four cases with WS who underwent cochlear implantation. These cases were assessed for age at implantation, clinical and radiological features, operative and perioperative course, and performance outcomes. Auditory perception and speech production ability were evaluated using categories of auditory performance (CAP), meaningful auditory integration scales (MAIS), and speech intelligibility rating (SIR) during the follow-up period. In this group of children with WS, with a minimum follow-up of 12 months, the CAP score ranged from 3 to 5, MAIS from 25 to 30, and SIR was 3. These scores are comparable with those of other cochlear implantees.

Waardenburg syndrome presenting with constipation since birth.

PubMed

Gupta, R; Sharma, S B; Mathur, P; Agrawal, L D

2014-12-01

Shah-Waardenburg syndrome is Waardenburg syndrome associated with Hirschsprung's disease. A 10-day-old full-term male neonate of Waardenburg syndrome presented with constipation since birth along with features of small bowel obstruction. Exploratory laparotomy revealed distended proximal jejunal and ileal loops along with microcolon; an ileostomy was performed. Postoperatively patient developed sepsis and died. Histopathology confirmed total colonic aganglionosis. Suspect familial Shah-Waardenburg syndrome in a neonate of Waardenburg syndrome presenting with constipation since birth or intestinal obstruction.

Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family

PubMed Central

de Aquino, Sibele-Nascimento; Paranaíba, Lívia-Maris-R.; Gomes, Andreia; dos-Santos-Neto, Pedro; Coletta, Ricardo-D.; Cardoso, Aline-Francoise; Frota, Ana-Cláudia; Martelli-Júnior, Hercílio

2016-01-01

Background The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. Material and Methods To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. Results The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. Conclusions These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. Clinical relevance: This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1. Key words:Waardenburg syndrome, hearing loss, oral manifestations, mutation. PMID:27031059

[Clinical and genetic investigation of families with Waardenburg syndrome type 2].

PubMed

Chen, H S; Liao, X B; Liu, Y L; He, C F; Zhang, H; Jiang, L; Feng, Y; Mei, L Y

2016-12-01

Objective: To investigate the clinical chacteration and molecular pathology of Waardenburg syndrome type 2 in seven families, and provide genetic diagnosis and hereditary counseling for family members. Method: Clinical data of seven families with WS2（14 patients）were collected. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of microphthalmia associated transcription factor (MITF), sex-determining region Y-box 10(SOX10), snail family zinc finger 2 (SNAI2) and endothelin receptor type B（EDNRB）were analyzed by polymerase chain reaction and DNA sequencing. Then the raw data was analyzed. Result: The most common manifestations of WS2 are sensorineural hearing loss(10/14,71.4%), freckle(7/14, 50.0%)，heterochromia iridis(6/14, 42.9%) and premature greying(5/14,35.7%). All the deafness phenotype is congenital, bilateral profound sensorineural hearing loss. Freckles phenotype is different from cutaneous pigment abnormalities of WS in Westerners. The heterozygous mutation, c.328C>T in exon 3 of the MITF gene was detected in the proband and all patients of pedigree 2. However, no pathological mutation of the relevant genes (SOX10,SNAI2 and EDNRB) was detected in other pedigrees. Conclusion: There are obvious variations in clinical features of WS, while freckles may be a special subtype of cutaneous pigment disturbances. The MITF gene mutation, R110X,is therefore considered the disease causing mutation in pedigree WS02.However, there are novel disease causing genes or copy number variations in Waardenburg syndrome type 2, which require further research. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Screening program for Waardenburg syndrome in Colombia: clinical definition and phenotypic variability.

PubMed

Tamayo, Marta L; Gelvez, Nancy; Rodriguez, Marcela; Florez, Silvia; Varon, Clara; Medina, David; Bernal, Jaime E

2008-04-15

A screening program to detect Waardenburg syndrome (WS) conducted between 2002 and 2005, among 1,763 deaf individuals throughout Columbia identified 95 affected individuals belonging to 95 families, giving a frequency of 5.38% of WS among the institutionalized deaf population. We confirmed the clinical diagnosis of WS in the 95 propositi and, through the family evaluation, we also identified 45 non-institutionalized affected relatives. Audiologic, ophthalmologic, and genetic studies were performed to confirm the diagnosis. Following the classification of the WS consortium, based on the Waardenburg Index (WI), to define the type of WS. We classified 62.1% of the propositi as WS2 and 37.9% as WS1. We present here the results of the study of clinical manifestations, analyzing the presence, severity, and symmetry of clinical findings among this affected population. Overall, among the 95 propositi, in addition to sensorineural deafness in all, the most frequent features were broad nasal root (58.9%), a first degree relative affected (37.9%), heterochromia irides (36.8%), skin hypopigmentation (31.6%), white forelock (28.0%), intense blue iris (27.4%), synophrys (12.6%), premature graying (10.5%), ptosis of the eyelids (9.5%), and hypoplasia alae nasi (1.1%). The majority of individuals had normal psychomotor development (87%), while the remaining 13% had developmental delay. Among the latter, 9.4% corresponded to WS2 and 3.6% to WS1. Our data confirm an interesting inter- and intrafamilial variability in the phenotypic manifestations as well as extremely variable expression. Copyright 2008 Wiley-Liss, Inc.

Three cases of Waardenburg syndrome type 2 in a Korean family.

PubMed

Choi, Joong Hyuk; Moon, Sung-Kyun; Lee, Ki Hwang; Lew, Ho Min; Chang, Yoon-Hee

2004-12-01

Waardenburg syndrome (WS) is a rare, autosomal dominant disorder characterized by sensorineural hearing loss, pigmentary disturbances of the skin, hair, and iris, and other developmental defects such as lateral displacement of both medial canthi and lacrimal puncta called dystopia canthorum. While mutations of the PAX3 (paired box) gene have been identified in about 99% of WS type 1 cases, WS type 2 is a heterogeneous group, with about 15% of cases caused by mutations in microphthalmia associated transcription factor (MITF). We have experienced three cases of typical WS type 2 in a Korean family, for whom full ocular examination and genetic studies were performed. The genetic studies revealed no mutation in either PAX3 or MITF genes. The genetic basis, as yet unknown for most cases of WS type 2, might be found with further investigation.

Heterogeneity in Waardenburg syndrome.

PubMed Central

Hageman, M J; Delleman, J W

1977-01-01

Heterogeneity of Waardenburg syndrome is demonstrated in a review of 1,285 patients from the literature and 34 previously unreported patients in five families in the Netherlands. The syndrome seems to consist of two genetically distinct entities that can be differentiated clinically: type I, Waardenburg syndrome with dystopia canthorum; and type II, Waardenburg syndrome without dystopia canthorum. Both types have an autosomal dominant mode of inheritance. The incidence of bilateral deafness in the two types of the syndrome was found in one-fourth with type I and about half of the patients with type II. This difference has important consequences for genetic counseling. Images Fig. 7 Fig. 8 Fig. 9 PMID:331943

Cytogenetic mapping of a novel locus for type II Waardenburg syndrome.

PubMed

Selicorni, Angelo; Guerneri, Silvana; Ratti, Antonia; Pizzuti, Antonio

2002-01-01

An Italian family in which Waardenburg syndrome type II (WS2) segregates together with a der(8) chromosome from a (4p;8p) balanced translocation was studied. Cytogenetic analysis by painting and subtelomeric probe hybridization positioned the chromosome 8 breakpoint at p22-pter. Fluorescence in situ hybridization analysis with yeast artificial chromosomes from a contig spanning the 8p21-pter region refined the breakpoint in an interval of less than 170 kb between markers WI-3823 and D8S1819. The only cloned gene for WS2 is that for microphtalmia (MITF) on chromosome 3p. In this family, MITF mutations were excluded by sequencing the whole coding region. The 8p23 region may represent a third locus for WS2 (WS2C).

Shah-Waardenburg Syndrome

PubMed Central

Mahmoudi, Abdelhalim; Rami, Mohamed; Khattala, Khalid; Elmadi, Aziz; Afifi, My Abderrahmane; Youssef, Bouabdallah

2013-01-01

Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. Is a very rare congenital disorder with variable clinical expression. This report describes a 4-day-old male newborn with Waardenburg's syndrome associated with aganglionosis of the colon and terminal ileum, and review the relevant literature for draws attention to the causal relationship between these two entities. PMID:23565307

Shah-Waardenburg syndrome.

PubMed

Mahmoudi, Abdelhalim; Rami, Mohamed; Khattala, Khalid; Elmadi, Aziz; Afifi, My Abderrahmane; Youssef, Bouabdallah

2013-01-01

Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. Is a very rare congenital disorder with variable clinical expression. This report describes a 4-day-old male newborn with Waardenburg's syndrome associated with aganglionosis of the colon and terminal ileum, and review the relevant literature for draws attention to the causal relationship between these two entities.

Possible Waardenburg syndrome with gastrointestinal anomalies.

PubMed Central

Nutman, J; Steinherz, R; Sivan, Y; Goodman, R M

1986-01-01

We describe a patient with possible Waardenburg syndrome associated with anal atresia and oesophageal atresia with tracheooesophageal fistula. Three other published cases with atretic gastrointestinal anomalies associated with the Waardenburg syndrome are reviewed. We conclude that the association between atretic lesions of the gastrointestinal tract and the Waardenburg syndrome may be a significant one. Images PMID:3712396

Novel PAX3 mutations causing Waardenburg syndrome type 1 in Tunisian patients.

PubMed

Trabelsi, Mediha; Nouira, Malek; Maazoul, Faouzi; Kraoua, Lilia; Meddeb, Rim; Ouertani, Ines; Chelly, Imen; Benoit, Valérie; Besbes, Ghazi; Mrad, Ridha

2017-12-01

Waardenburg syndrome (WS) is an auditory-pigmentary disease characterized by a clinical and genetic variability. WS is classified into four types depending on the presence or absence of additional symptoms: WS1, WS2, WS3 and WS4. Type 1 and 3 are mostly caused by PAX3 mutations, while type 2 and type 4 are genetically heterogeneous. The aims of this study are to confirm the diagnostic of WS1 by the sequencing of PAX3 gene and to evaluate the genotype phenotype correlation. A clinical classification was established for 14 patients WS, as proposed by the Waardenburg Consortium, and noted a predominance of type 1 and type 2 with 6 patients WS1, 7 patients WS2 and 1 patient WS3. A significant inter and intra-familial clinical heterogeneity was also observed. A sequencing of PAX3 gene in the 6 patients WS1 confirmed the diagnosis in 4 of them by revealing three novel mutations that modify two functional domains of the protein: the c.942delC; the c.933_936dupTTAC and the c.164delTCCGCCACA. These three variations are most likely responsible for the phenotype, however their pathogenic effects need to be confirmed by functional studies. The MLPA analysis of the 2 patients who were sequence negative for PAX3 gene revealed, in one of them, a heterozygous deletion of exons 5 to 9 confirming the WS1 diagnosis. Both clinical and molecular approaches led to the conclusion that there is a lack of genotype-phenotype correlation in WS1, an element that must be taken into account in genetic counseling. The absence of PAX3 mutation in one patient WS1 highlights the fact that the clinical classification is sometimes insufficient to distinguish WS1 from other types WS hence the interest of sequencing the other WS genes in this patient. Copyright © 2017 Elsevier B.V. All rights reserved.

A Novel Mutation in the Endothelin B Receptor Gene in a Moroccan Family with Shah-Waardenburg Syndrome

PubMed Central

Doubaj, Yassamine; Pingault, Véronique; Elalaoui, Siham C.; Ratbi, Ilham; Azouz, Mohamed; Zerhouni, Hicham; Ettayebi, Fouad; Sefiani, Abdelaziz

2015-01-01

Waardenburg syndrome (WS) is a neurocristopathy disorder combining sensorineural deafness and pigmentary abnormalities. The presence of additional signs defines the 4 subtypes. WS type IV, also called Shah-Waardenburg syndrome (SWS), is characterized by the association with congenital aganglionic megacolon (Hirschsprung disease). To date, 3 causative genes have been related to this congenital disorder. Mutations in the EDNRB and EDN3 genes are responsible for the autosomal recessive form of SWS, whereas SOX10 mutations are inherited in an autosomal dominant manner. We report here the case of a 3-month-old Morrocan girl with WS type IV, born to consanguineous parents. The patient had 3 cousins who died in infancy with the same symptoms. Molecular analysis by Sanger sequencing revealed the presence of a novel homozygous missense mutation c.1133A>G (p.Asn378Ser) in the EDNRB gene. The proband's parents as well as the parents of the deceased cousins are heterozygous carriers of this likely pathogenic mutation. This molecular diagnosis allows us to provide genetic counseling to the family and eventually propose prenatal diagnosis to prevent recurrence of the disease in subsequent pregnancies. PMID:25852447

A novel mutation in the endothelin B receptor gene in a moroccan family with shah-waardenburg syndrome.

PubMed

Doubaj, Yassamine; Pingault, Véronique; Elalaoui, Siham C; Ratbi, Ilham; Azouz, Mohamed; Zerhouni, Hicham; Ettayebi, Fouad; Sefiani, Abdelaziz

2015-02-01

Waardenburg syndrome (WS) is a neurocristopathy disorder combining sensorineural deafness and pigmentary abnormalities. The presence of additional signs defines the 4 subtypes. WS type IV, also called Shah-Waardenburg syndrome (SWS), is characterized by the association with congenital aganglionic megacolon (Hirschsprung disease). To date, 3 causative genes have been related to this congenital disorder. Mutations in the EDNRB and EDN3 genes are responsible for the autosomal recessive form of SWS, whereas SOX10 mutations are inherited in an autosomal dominant manner. We report here the case of a 3-month-old Morrocan girl with WS type IV, born to consanguineous parents. The patient had 3 cousins who died in infancy with the same symptoms. Molecular analysis by Sanger sequencing revealed the presence of a novel homozygous missense mutation c.1133A>G (p.Asn378Ser) in the EDNRB gene. The proband's parents as well as the parents of the deceased cousins are heterozygous carriers of this likely pathogenic mutation. This molecular diagnosis allows us to provide genetic counseling to the family and eventually propose prenatal diagnosis to prevent recurrence of the disease in subsequent pregnancies.

Anisometropic amblyopia in a case of type 2 Waardenburg syndrome.

PubMed

Akal, Ali; Göncü, Tugba; Boyaci, Nurefsan; Yılmaz, Ömer Faruk

2013-12-18

This study presents a case of an 8-year-old boy with iris heterochromia and anisometropic amblyopia who was diagnosed with Waardenburg syndrome (WS) type 2. An ophthalmic examination revealed iris heterochromia and anisometropic amblyopia in our patient. In the systemic examination, a white forelock and vitiligo on the arms and body were observed and neurosensory hearing loss was revealed, for which the patient used hearing aids. Identification and typing of patients with WS is crucial to address neurosensory hearing loss, glaucoma and fundus changes. While it might be challenging to communicate with a patient with speech and hearing problems, visual acuity should be examined carefully and probable amblyopia should be identified. Anterior segment changes and signs of glaucoma should also be evaluated in detail.

Anisometropic amblyopia in a case of type 2 Waardenburg syndrome

PubMed Central

Akal, Ali; Göncü, Tugba; Boyaci, Nurefsan; Yılmaz, Ömer Faruk

2013-01-01

This study presents a case of an 8-year-old boy with iris heterochromia and anisometropic amblyopia who was diagnosed with Waardenburg syndrome (WS) type 2. An ophthalmic examination revealed iris heterochromia and anisometropic amblyopia in our patient. In the systemic examination, a white forelock and vitiligo on the arms and body were observed and neurosensory hearing loss was revealed, for which the patient used hearing aids. Identification and typing of patients with WS is crucial to address neurosensory hearing loss, glaucoma and fundus changes. While it might be challenging to communicate with a patient with speech and hearing problems, visual acuity should be examined carefully and probable amblyopia should be identified. Anterior segment changes and signs of glaucoma should also be evaluated in detail. PMID:24351514

Cochlear implants in Waardenburg syndrome.

PubMed

Cullen, Robert D; Zdanski, Carlton; Roush, Patricia; Brown, Carolyn; Teagle, Holly; Pillsbury, Harold C; Buchman, Craig

2006-07-01

Waardenburg syndrome is an autosomal-dominant syndrome characterized by dystopia canthorum, hyperplasia of the eyebrows, heterochromia irides, a white forelock, and sensorineural hearing loss in 20% to 55% of patients. This patient population accounts for approximately 2% of congenitally deaf children. The purpose of this retrospective case review was to describe the outcomes for those children with Waardenburg syndrome who have undergone cochlear implantation. Pediatric cochlear implant recipients with documented evidence of Waardenburg syndrome underwent retrospective case review. All patients received their cochlear implants at the study institution followed by outpatient auditory habilitation. Charts were reviewed for etiology and duration of deafness, age at time of cochlear implantation, perioperative complications, duration of use, and performance outcomes. Results of standard tests batteries for speech perception and production administered as a part of the patients' auditory habilitation were reviewed. Seven patients with Waardenburg syndrome and cochlear implants were identified. The average age at implantation was 37 months (range, 18-64 months) and the average duration of use was 69 months (range, 12-143 months). All of these patients are active users of their devices and perform very well after implantation. There were no major complications in this small group of patients. Children with congenital sensorineural hearing loss without other comorbidities (e.g., developmental delay, inner ear malformations) perform well when they receive cochlear implantation and auditory habilitation. Patients with Waardenburg syndrome can be expected to have above-average performance after cochlear implantation.

[Waardenburg syndrome. A heterogenic disorder with variable penetrance].

PubMed

Apaydin, F; Bereketoglu, M; Turan, O; Hribar, K; Maassen, M M; Günhan, O; Zenner, H-P; Pfister, M

2004-06-01

Waardenburg syndrome (WS) is an autosomal dominant disorder characterised by pigmentary anomalies of the skin, hairs, eyes and various defects of other neural crest derived tissues. It accounts for over 2% of congenital hearing impairment. At least four types are recognized on the basis of clinical and genetic criteria. Based on a screening of congenitally hearing impaired children, 12 families with WS type II were detected. Of special interest was the phenotype of these families, in particular the reduced penetrance of hearing impairment within the families. In all cases a high variability of the disease phenotype was detected and the penetrance of the clinical traits varied accordingly. Therefore, it is not possible to predict the clinical phenotype even in a single family. Based on these studies, we plan to identify the pathogenetic cause of the disease in order to perform a detailed genotype/phenotype analysis.

Waardenburg syndrome type 2: an orthodontic perspective.

PubMed

Şuhani, Raluca Diana; Şuhani, Mihai Flaviu; Muntean, Alexandrina; Mesaroş, Michaela Florica; Badea, Mîndra Eugenia

2015-01-01

Waardenburg syndrome is a rare form of neurocristopathy. It is a disorder in the development of neural crest cells, caused by an altered cellular migration during the embryonic phase. That alteration causes an association of different abnormalities such as pigmentary disturbances of the hair, iris, skin, stria vascularis of the cochlea, dystopia canthorum and sensorineural hearing loss. We report a case of a 14-year-old Romanian male, with a family history of Waardenburg syndrome (mother) and Usher syndrome (father - congenitally sensorineural hearing loss and retinal degeneration). The case particularities are: the correlation between malocclusion and Waardenburg syndrome due to hypoplastic alae nasi and also factors that produced hearing loss, which could be Waardenburg syndrome, Usher syndrome or the presence of the connexin 26 (W24X) gene mutation.

Worldwide distribution of Waardenburg syndrome.

PubMed

Nayak, Chetan S; Isaacson, Glenn

2003-09-01

To clarify the multiracial occurrence of Waardenburg syndrome, we present a case series and literature review. A computerized review of the English-language literature was conducted to assess the distribution of reported occurrences of Waardenburg syndrome in populations around the world. We detail the clinical features of 2 family cohorts: one of Western European origin and the other from South Asia. A computerized literature review found sporadic cases of the syndrome in many ethnic groups, including Japanese, Taiwanese, and Middle Eastern families. The highest reported incidence is among Kenyan Africans. Waardenburg syndrome accounts for between 2% and 5% of cases of congenital deafness. It was first described in Northern European cohorts and is widely identified in fair-skinned populations. We hope to raise awareness of the worldwide distribution of this important cause of hearing loss.

[Atypical manifestations in familial type 1 Waardenburg syndrome].

PubMed

Sans, B; Calvas, P; Bazex, J

1998-01-01

Waardenburg syndrome is an uncommon genetic disorder. Four clinical types are recognized. Three responsible genes have been identified (PAX 3: for type I syndrome, MITF and EDN3 for types II and IV respectively). We report the case of a patient with Waardenburg type I morphotype who had atypical neurological manifestations. Decisive elements for diagnosis were the presence of Waardenburg syndrome in the family and, in affected kin, a mutation causing a shift in PAX 3 gene reading. This case confirms the variability of Waardenburg signs within one family. The association of unusual neurological manifestations in the proband suggested that Vogt Koyanagi Harada disease may have been associated and may show some relationship with familial Waardenburg syndrome.

EDNRB mutations cause Waardenburg syndrome type II in the heterozygous state.

PubMed

Issa, Sarah; Bondurand, Nadege; Faubert, Emmanuelle; Poisson, Sylvain; Lecerf, Laure; Nitschke, Patrick; Deggouj, Naima; Loundon, Natalie; Jonard, Laurence; David, Albert; Sznajer, Yves; Blanchet, Patricia; Marlin, Sandrine; Pingault, Veronique

2017-05-01

Waardenburg syndrome (WS) is a genetic disorder characterized by sensorineural hearing loss and pigmentation anomalies. The clinical definition of four WS types is based on additional features due to defects in structures mostly arising from the neural crest, with type I and type II being the most frequent. While type I is tightly associated to PAX3 mutations, WS type II (WS2) remains partly enigmatic with mutations in known genes (MITF, SOX10) accounting for only 30% of the cases. We performed exome sequencing in a WS2 index case and identified a heterozygous missense variation in EDNRB. Interestingly, homozygous (and very rare heterozygous) EDNRB mutations are already described in type IV WS (i.e., in association with Hirschsprung disease [HD]) and heterozygous mutations in isolated HD. Screening of a WS2 cohort led to the identification of an overall of six heterozygous EDNRB variations. Clinical phenotypes, pedigrees and molecular segregation investigations unraveled a dominant mode of inheritance with incomplete penetrance. In parallel, cellular and functional studies showed that each of the mutations impairs the subcellular localization of the receptor or induces a defective downstream signaling pathway. Based on our results, we now estimate EDNRB mutations to be responsible for 5%-6% of WS2. © 2017 Wiley Periodicals, Inc.

Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome?

PubMed

Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R; Matsushita, Mark; Raskind, Wendy H

2008-07-15

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair, and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. 2008 Wiley-Liss, Inc.

Waardenburg syndrome: a rare cause of inherited neuropathy due to SOX10 mutation.

PubMed

Bogdanova-Mihaylova, Petya; Alexander, Michael D; Murphy, Raymond P J; Murphy, Sinéad M

2017-09-01

Waardenburg syndrome (WS) is a rare disorder comprising sensorineural deafness and pigmentation abnormalities. Four distinct subtypes are defined based on the presence or absence of additional symptoms. Mutations in six genes have been described in WS. SOX10 mutations are usually associated with a more severe phenotype of WS with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, and Hirschsprung disease. Here we report a 32-year-old man with a novel heterozygous missense variant in SOX10 gene, who presented with congenital deafness, Hirschsprung disease, iris heterochromia, foot deformity, and intermediate conduction velocity length-dependent sensorimotor neuropathy. This case highlights that the presence of other non-neuropathic features in a patient with presumed hereditary neuropathy should alert the clinician to possible atypical rare causes. © 2017 Peripheral Nerve Society.

Hearing dysfunction in heterozygous Mitf(Mi-wh) /+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome.

PubMed

Ni, Christina; Zhang, Deming; Beyer, Lisa A; Halsey, Karin E; Fukui, Hideto; Raphael, Yehoash; Dolan, David F; Hornyak, Thomas J

2013-01-01

The human deafness-pigmentation syndromes, Waardenburg syndrome (WS) type 2a, and Tietz syndrome are characterized by profound deafness but only partial cutaneous pigmentary abnormalities. Both syndromes are caused by mutations in MITF. To illuminate differences between cutaneous and otic melanocytes in these syndromes, their development and survival in heterozygous Microphthalmia-White (Mitf(Mi-wh) /+) mice were studied and hearing function of these mice characterized. Mitf(Mi-wh) /+ mice have a profound hearing deficit, characterized by elevated auditory brainstem response thresholds, reduced distortion product otoacoustic emissions, absent endocochlear potential, loss of outer hair cells, and stria vascularis abnormalities. Mitf(Mi-wh) /+ embryos have fewer melanoblasts during embryonic development than their wild-type littermates. Although cochlear melanocytes are present at birth, they disappear from the Mitf(Mi-wh) /+ cochlea between P1 and P7. These findings may provide insight into the mechanism of melanocyte and hearing loss in human deafness-pigmentation syndromes such as WS and Tietz syndrome and illustrate differences between otic and follicular melanocytes. © 2012 John Wiley & Sons A/S.

Because You Asked about Waardenburg Syndrome.

ERIC Educational Resources Information Center

National Inst. on Deafness and Other Communications Disorders, Bethesda, MD.

This pamphlet uses a question-and-answer format to provide information about Waardenburg syndrome, an inherited disorder often characterized by varying degrees of hearing loss and changes in skin and hair pigmentation. The pamphlet covers: causes of Waardenburg syndrome. characteristics, types, research being done, ways to help in research…

Screening of MITF and SOX10 Regulatory Regions in Waardenburg Syndrome Type 2

PubMed Central

Baral, Viviane; Chaoui, Asma; Watanabe, Yuli; Goossens, Michel; Attie-Bitach, Tania; Marlin, Sandrine; Pingault, Veronique; Bondurand, Nadege

2012-01-01

Waardenburg syndrome (WS) is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2) can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE) and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy. PMID:22848661

Screening of MITF and SOX10 regulatory regions in Waardenburg syndrome type 2.

PubMed

Baral, Viviane; Chaoui, Asma; Watanabe, Yuli; Goossens, Michel; Attie-Bitach, Tania; Marlin, Sandrine; Pingault, Veronique; Bondurand, Nadege

2012-01-01

Waardenburg syndrome (WS) is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2) can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE) and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy.

Genetic and phenotypic heterogeneity in Chinese patients with Waardenburg syndrome type II.

PubMed

Yang, Shuzhi; Dai, Pu; Liu, Xin; Kang, Dongyang; Zhang, Xin; Yang, Weiyan; Zhou, Chengyong; Yang, Shiming; Yuan, Huijun

2013-01-01

Waardenburg Syndrome (WS) is an autosomal-dominant disorder characterized by sensorineural hearing loss and pigmentary abnormalities of the eyes, hair, and skin. Microphthalmia-associated transcription factor (MITF) gene mutations account for about 15% of WS type II (WS2) cases. To date, fewer than 40 different MITF gene mutations have been identified in human WS2 patients, and few of these were of Chinese descent. In this study, we report clinical findings and mutation identification in the MITF gene of 20 Chinese WS2 patients from 14 families. A high level of clinical variability was identified. Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients. Five affected individuals (5/20, 25.0%) had numerous brown freckles on the face, trunk, and limb extremities. Mutation screening of the MITF gene identified five mutations: c.20A>G, c.332C>T, c.647_649delGAA, c.649A>G, and c.763C>T. The total mutational frequency of the MITF gene was 21.4% (3/14), which is significantly higher than the 15.0% observed in the fair-skinned WS2 population. Our results indicate that MITF mutations are relatively common among Chinese WS2 patients.

Waardenburg syndrome and myelomeningocele in a family.

PubMed Central

Chatkupt, S; Chatkupt, S; Johnson, W G

1993-01-01

We report the first family with Waardenburg syndrome type 1 and myelomeningocele in which more than one subject was affected with both disorders. The possible association is discussed. Prenatal screening for myelomeningocele is suggested for a family with Waardenburg syndrome type 1. Images PMID:8423616

Heterozygous deletion at the SOX10 gene locus in two patients from a Chinese family with Waardenburg syndrome type II.

PubMed

Wenzhi, He; Ruijin, Wen; Jieliang, Li; Xiaoyan, Ma; Haibo, Liu; Xiaoman, Wang; Jiajia, Xian; Shaoying, Li; Shuanglin, Li; Qing, Li

2015-10-01

Waardenburg syndrome (WS) is a rare disease characterized by sensorineural deafness and pigment disturbance. To date, almost 100 mutations have been reported, but few reports on cases with SOX10 gene deletion. The inheritance pattern of SOX10 gene deletion is still unclear. Our objective was to identify the genetic causes of Waardenburg syndrome type II in a two-generation Chinese family. Clinical evaluations were conducted in both of the patients. Microarray analysis and multiplex ligation-dependent probe amplification (MLPA) were performed to identify disease-related copy number variants (CNVs). DNA sequencing of the SOX10, MITF and SNAI2 genes was performed to identify the pathogenic mutation responsible for WS2. A 280kb heterozygous deletion at the 22q13.1 chromosome region (including SOX10) was detected in both of the patients. No mutation was found in the patients, unaffected family members and 30 unrelated healthy controls. This report is the first to describe SOX10 heterozygous deletions in Chinese WS2 patients. Our result conform the thesis that heterozygous deletions at SOX10 is an important pathogenicity for WS, and present as autosomal dominant inheritance. Nevertheless, heterozygous deletion of the SOX10 gene would be worth investigating to understand their functions and contributions to neurologic phenotypes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evidence suggesting digenic inheritance of Waardenburg syndrome type II with ocular albinism.

PubMed

Chiang, Pei-Wen; Spector, Elaine; McGregor, Tracy L

2009-12-01

Waardenburg syndrome (WS) is a series of auditory-pigmentary disorders inherited in an autosomal dominant manner. In most patients, WS2 results from mutations in the MITF gene. MITF encodes a basic helix-loop-helix transcription factor that activates transcription of tyrosinase and other melanocyte proteins. The clinical presentation of WS is highly variable, and we believe that Tietz syndrome and WS2 with ocular albinism (OA) are likely two variations of WS2 due to the presence of modifiers. One family with a molecular diagnosis of WS2 co-segregating with OA has previously been reported. A digenic mutation mechanism including both a MITF mutation and the TYR(R402Q) hypomorphic allele was proposed to be the cause of OA in this family. Here, we present a second WS2 family with OA and provide evidence suggesting the TYR(R402Q) allele does not cause OA in this family. We hypothesize the presence of a novel OCA3 mutation together with the MITF del p.R217 mutation account for the OA phenotype in this family. Since MITF is a transcription factor for pigmentation genes, a mutation in MITF plus a heterozygous mutation in OCA3 together provide an adverse effect crossing a quantitative threshold; therefore, WS2 with OA occurs. We have hypothesized previously that the clinical spectrum and mutation mechanism of OCA depend on the pigmentation threshold of an affected individual. This unique family has provided further evidence supporting this hypothesis. We suggest that by studying OCA patients alongside WS patients with various pigmentation profiles we can facilitate further understanding of the pigmentation pathway.

Waardenburg syndrome with familial unilateral renal agenesis: a new syndrome variant?

PubMed

Webb, Katie M; Smith, Alisha J; Dansby, Linda M; Diskin, Charles J

2015-06-01

A 64-year-old man with Waardenburg syndrome presented with anuria and was subsequently discovered by renal ultrasound to have unilateral renal agenesis. The patient is one of three generations with incidental finding of renal agenesis also marked by the presence of Waardenburg syndrome. To our knowledge, there has been no mention elsewhere in the scientific literature of a variant of Waardenburg syndrome with associated renal agenesis. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.

Molecular and clinical characterization of Waardenburg syndrome type I in an Iranian cohort with two novel PAX3 mutations.

PubMed

Jalilian, Nazanin; Tabatabaiefar, Mohammad Amin; Farhadi, Mohammad; Bahrami, Tayeb; Emamdjomeh, Hesam; Noori-Daloii, Mohammad Reza

2015-12-15

Waardenburg syndrome (WS) is a disease of abnormal neural-crest derived melanocyte development characterized by hearing loss and pigmentary disturbances in hair, eyes and skin. WS is subdivided into four major types, WS1-WS4, where WS1 is recognized by the presence of dystopia canthorum, with PAX3 being the only known gene involved. This study aimed at investigating PAX3 mutations and clinical characteristics of WS1 in a group of Iranian patients. A total of 12 WS1 patients from four unrelated Iranian families were enrolled. Waardenburg consortium guidelines were used for WS1 diagnosis. A detailed family history was traced and a thorough clinical examination was performed for all participants. Furthermore, WS1 patients underwent screening for PAX3 mutations using PCR-sequencing. Dystopia canthorum, broad high nasal root and synophrys were observed in all patients. Early graying, hair discoloration, hypoplastic blue eyes (characteristic brilliant blue iris) and hearing loss were the most common features observed, while heterochromia iridis was the least frequently observed sign among the studied Iranian WS1 patients. Genetic analysis of PAX3 revealed four mutations including c.667C>T, c.784C>T, c.951delT and c.451+3A>C. Two of the four mutations reported here (c.951delT and c.451+3A>C) are being reported for the first time in this study. Our data provide insight into genotypic and phenotypic spectrum of WS1 in an Iranian series of patients. Our results expand the spectrum of PAX3 mutations and may have implications for the genetic counseling of WS in Iran. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetic analysis of a Chinese family with members affected with Usher syndrome type II and Waardenburg syndrome type IV.

PubMed

Wang, Xueling; Lin, Xiao-Jiang; Tang, Xiangrong; Chai, Yong-Chuan; Yu, De-Hong; Chen, Dong-Ye; Wu, Hao

2017-11-01

The purpose of this study was to identify the genetic causes of a family presenting with multiple symptoms overlapping Usher syndrome type II (USH2) and Waardenburg syndrome type IV (WS4). Targeted next-generation sequencing including the exon and flanking intron sequences of 79 deafness genes was performed on the proband. Co-segregation of the disease phenotype and the detected variants were confirmed in all family members by PCR amplification and Sanger sequencing. The affected members of this family had two different recessive disorders, USH2 and WS4. By targeted next-generation sequencing, we identified that USH2 was caused by a novel missense mutation, p.V4907D in GPR98; whereas WS4 due to p.V185M in EDNRB. This is the first report of homozygous p.V185M mutation in EDNRB in patient with WS4. This study reported a Chinese family with multiple independent and overlapping phenotypes. In condition, molecular level analysis was efficient to identify the causative variant p.V4907D in GPR98 and p.V185M in EDNRB, also was helpful to confirm the clinical diagnosis of USH2 and WS4. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of a de novo mutation of SOX10 in a Chinese patient with Waardenburg syndrome type IV.

PubMed

Liang, Fenghe; Zhao, Min; Fan, Lynn; Zhang, Hongyan; Shi, Yang; Han, Rui; Qu, Chunyan

2016-12-01

Waardenburg syndrome is a rare genetic disorder, characterized by the association of sensorineural hearing loss and pigmentation abnormalities. Four subtypes have been classified. The present study aimed to analyze the clinical feature and investigate the genetic cause for a Chinese case of Waardenburg type IV (WS4). The patient and his family members were subjected to mutation detection in the candidate gene SOX10 by Sanger sequencing. The patient has the clinical features of WS4, including sensorineural hearing loss, bright blue irides, premature graying of the hair and Hirschsprung disease. A novel heterozygous frameshift mutation, c.752_753ins7 (p.Gly252Alafs*31) in the exon 5 of SOX10 was detected in the patient, but not found in the unaffected family members and 100 normal controls. This mutation results in a premature stop codon 31 amino acid downstream. The novel mutation c.752_753ins7 (p.Gly252Alafs*31) arose de novo and was considered as the cause of WS4 in the proband. This study further characterized the molecular complexity of WS4 and provided a clinical case for genotype-phenotype correlation studies of different phenotypes caused by SOX10 mutations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Genetic and Phenotypic Heterogeneity in Chinese Patients with Waardenburg Syndrome Type II

PubMed Central

Yang, Shuzhi; Dai, Pu; Liu, Xin; Kang, Dongyang; Zhang, Xin; Yang, Weiyan; Zhou, Chengyong; Yang, Shiming; Yuan, Huijun

2013-01-01

Waardenburg Syndrome (WS) is an autosomal-dominant disorder characterized by sensorineural hearing loss and pigmentary abnormalities of the eyes, hair, and skin. Microphthalmia-associated transcription factor (MITF) gene mutations account for about 15% of WS type II (WS2) cases. To date, fewer than 40 different MITF gene mutations have been identified in human WS2 patients, and few of these were of Chinese descent. In this study, we report clinical findings and mutation identification in the MITF gene of 20 Chinese WS2 patients from 14 families. A high level of clinical variability was identified. Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients. Five affected individuals (5/20, 25.0%) had numerous brown freckles on the face, trunk, and limb extremities. Mutation screening of the MITF gene identified five mutations: c.20A>G, c.332C>T, c.647_649delGAA, c.649A>G, and c.763C>T. The total mutational frequency of the MITF gene was 21.4% (3/14), which is significantly higher than the 15.0% observed in the fair-skinned WS2 population. Our results indicate that MITF mutations are relatively common among Chinese WS2 patients. PMID:24194866

Wnt signaling pathway involvement in genotypic and phenotypic variations in Waardenburg syndrome type 2 with MITF mutations.

PubMed

Wang, Xue-Ping; Liu, Ya-Lan; Mei, Ling-Yun; He, Chu-Feng; Niu, Zhi-Jie; Sun, Jie; Zhao, Yu-Lin; Feng, Yong; Zhang, Hua

2018-05-01

Mutation in the gene encoding microphthalmia-associated transcription factor (MITF) lead to Waardenburg syndrome 2 (WS2), an autosomal dominantly inherited syndrome with auditory-pigmentary abnormalities, which is clinically and genetically heterogeneous. Haploinsufficiency may be the underlying mechanism for WS2. However, the mechanisms explaining the genotypic and phenotypic variations in WS2 caused by MITF mutations are unclear. A previous study revealed that MITF interacts with LEF-1, an important factor in the Wnt signaling pathway, to regulate its own transcription through LEF-1-binding sites on the MITF promoter. In this study, four different WS2-associated MITF mutations (p.R217I, p.R217G, p.R255X, p.R217del) that are associated with highly variable clinical features were chosen. According to the results, LEF-1 can activate the expression of MITF on its own, but MITF proteins inhibited the activation. This inhibition weakens when the dosage of MITF is reduced. Except for p.R217I, p.R255X, p.R217G, and p.R217del lose the ability to activate TYR completely and do not inhibit the LEF-1-mediated activation of the MITF-M promoter, and the haploinsufficiency created by mutant MITF can be overcome; correspondingly, the mutants' associated phenotypes are less severe than that of p.R217I. The dominant negative of p.R217del made it have a second-most severe phenotype. This study's data imply that MITF has a negative feedback loop of regulation to stabilize MITF gene dosage that involves the Wnt signaling pathway and that the interaction of MITF mutants with this pathway drives the genotypic and phenotypic differences observed in Waardenburg syndrome type 2 associated with MITF mutations.

Identification and functional analysis of a novel mutation in the PAX3 gene associated with Waardenburg syndrome type I.

PubMed

Niu, Zhijie; Li, Jiada; Tang, Fen; Sun, Jie; Wang, Xueping; Jiang, Lu; Mei, Lingyun; Chen, Hongsheng; Liu, Yalan; Cai, Xinzhang; Feng, Yong; He, Chufeng

2018-02-05

Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant genetic disorder of neural crest cells (NCC) characterized by congenital sensorineural hearing loss, dystopia canthorum, and abnormal iris pigmentation. WS1 is due to loss-of-function mutations in paired box gene 3 (PAX3). Here, we identified a novel PAX3 mutation (c.808C>G, p.R270G) in a three-generation Chinese family with WS1, and then analyzed its in vitro activities. The R270G PAX3 retained nuclear distribution and normal DNA-binding ability; however, it failed to activate MITF promoter, suggesting that haploinsufficiency may be the underlying mechanism for the mild WS1 phenotype of the study family. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II.

PubMed

Zhang, Hua; Chen, Hongsheng; Luo, Hunjin; An, Jing; Sun, Lin; Mei, Lingyun; He, Chufeng; Jiang, Lu; Jiang, Wen; Xia, Kun; Li, Jia-Da; Feng, Yong

2012-03-01

Waardenburg syndrome (WS) is an auditory-pigmentary disorder resulting from melanocyte defects, with varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four subtypes (WS1-WS4) based on additional symptoms. PAX3 and SOX10 are two transcription factors that can activate the expression of microphthalmia-associated transcription factor (MITF), a critical transcription factor for melanocyte development. Mutations of PAX3 are associated with WS1 and WS3, while mutations of SOX10 cause WS2 and WS4. Recently, we identified some novel WS-associated mutations in PAX3 and SOX10 in a cohort of Chinese WS patients. Here, we further identified an E248fsX30 SOX10 mutation in a family of WS2. We analyzed the subcellular distribution, expression and in vitro activity of two PAX3 mutations (p.H80D, p.H186fsX5) and four SOX10 mutations (p.E248fsX30, p.G37fsX58, p.G38fsX69 and p.R43X). Except H80D PAX3, which retained partial activity, the other mutants were unable to activate MITF promoter. The H80D PAX3 and E248fsX30 SOX10 were localized in the nucleus as wild type (WT) proteins, whereas the other mutant proteins were distributed in both cytoplasm and nucleus. Furthermore, E248fsX30 SOX10 protein retained the DNA-binding activity and showed dominant-negative effect on WT SOX10. However, E248fsX30 SOX10 protein seems to decay faster than the WT one, which may underlie the mild WS2 phenotype caused by this mutation.

Outcomes and special considerations of cochlear implantation in waardenburg syndrome.

PubMed

Kontorinis, Georgios; Lenarz, Thomas; Giourgas, Alexandros; Durisin, Martin; Lesinski-Schiedat, Anke

2011-08-01

The objective of this study was a state-of-the-art analysis of cochlear implantation in patients with Waardenburg syndrome (WS). Twenty-five patients with WS treated with cochlear implants in our department from 1990 to 2010. The 25 patients with WS underwent 35 cochlear implantations. Hearing outcome was evaluated using HSM sentence test in 65 dB in quiet, Freiburg Monosyllabic Test, and categories of auditory performance for children and compared with that of a control group. Anatomic abnormalities of the inner ear were examined using magnetic resonance imaging and computed tomography of the temporal bones. The mean follow-up time was 8.3 years (range, 0.3-18.3 yr). The majority achieved favorable postimplantation performance with mean HSM scores of 75.3% (range, 22.6%-99%) and Freiburg Monosyllabic Test scores of 67.8% (range, 14%-95%). However, in 4 cases, the results were less satisfactory. The comparison with the control group did not reveal any statistical significance (p = 0.56). In 6 patients (24%), behavioral disorders caused temporary difficulties during the rehabilitation procedure. Except of isolated large vestibule in 1 patient, the radiological assessment of the 50 temporal bones did not reveal any temporal bone abnormalities. Most patients with WS performed well with cochlear implants. However, WS is related to behavioral disorders that may cause temporary rehabilitation difficulties. Finally, temporal bone malformations that could affect cochlear implantation are notcharacteristic of WS.

Electrodiagnostic findings in a patient with Waardenburg syndrome.

PubMed

Ahmed, Aiesha; Simmons, Zachary

2009-09-01

Waardenburg syndrome is associated with a variety of clinical features, which may include polyneuropathy. We describe a patient with Waardenburg syndrome type 2 and provide detailed electrodiagnostic findings, thus complementing the biopsy data and brief descriptions of nerve conduction studies found in the literature.

A novel missense mutation of the paired box 3 gene in a Turkish family with Waardenburg syndrome type 1

PubMed Central

Ozturk, A.Taylan; Adibelli, Hamit; Unal, Nurettin; Tukun, Ajlan

2013-01-01

Purpose Screening of mutations in the paired box 3 (PAX3) gene in three generations of a Turkish family with Waardenburg syndrome type 1 (WS1). Methods WS1 was diagnosed in a 13-month-old girl according to the WS Consortium criteria. Detailed family history of the proband revealed eight affected members in three generations. Routine clinical and audiological examination and ophthalmologic evaluation were performed on eight affected and five healthy members of the study family. Dystopia canthorum was detected in all affected patients; however, a brilliant blue iris was present in five patients who also had mild retinal hypopigmentation. Genomic DNA was extracted from the peripheral blood of affected and unaffected individuals in the family as well as 50 unrelated healthy volunteers. All coding exons and adjacent intronic regions of PAX3 were sequenced directly. Results A novel missense heterozygous c.788T>G mutation was identified in eight patients. This nucleotide alteration was not found in unaffected members of the study family or in the 50 unrelated control subjects. The mutation causes V263G amino-acid substitution in the homeodomain of the PAX3 protein, which represents the 45th residue of helix 3. Conclusions We identified a novel missense c.788T>G mutation in PAX3 in a family with Waardenburg syndrome with intrafamilial phenotypic heterogeneity. PMID:23378733

A novel missense mutation of the paired box 3 gene in a Turkish family with Waardenburg syndrome type 1.

PubMed

Hazan, Filiz; Ozturk, A Taylan; Adibelli, Hamit; Unal, Nurettin; Tukun, Ajlan

2013-01-01

Screening of mutations in the paired box 3 (PAX3) gene in three generations of a Turkish family with Waardenburg syndrome type 1 (WS1). WS1 was diagnosed in a 13-month-old girl according to the WS Consortium criteria. Detailed family history of the proband revealed eight affected members in three generations. Routine clinical and audiological examination and ophthalmologic evaluation were performed on eight affected and five healthy members of the study family. Dystopia canthorum was detected in all affected patients; however, a brilliant blue iris was present in five patients who also had mild retinal hypopigmentation. Genomic DNA was extracted from the peripheral blood of affected and unaffected individuals in the family as well as 50 unrelated healthy volunteers. All coding exons and adjacent intronic regions of PAX3 were sequenced directly. A novel missense heterozygous c.788T>G mutation was identified in eight patients. This nucleotide alteration was not found in unaffected members of the study family or in the 50 unrelated control subjects. The mutation causes V263G amino-acid substitution in the homeodomain of the PAX3 protein, which represents the 45(th) residue of helix 3. We identified a novel missense c.788T>G mutation in PAX3 in a family with Waardenburg syndrome with intrafamilial phenotypic heterogeneity.

A novel mutation in the PAX3 gene causes Waardenburg syndrome type I in an Iranian family.

PubMed

Jalilian, Nazanin; Tabatabaiefar, Mohammad Amin; Farhadi, Mohammad; Bahrami, Tayyeb; Noori-Daloii, Mohammad Reza

2015-10-01

Sensorineural hearing impairment (HI) is one of the most frequent congenital defects, with a prevalence of 1 in 500 among neonates. Although there are over 400 syndromes involving HI, most cases of HI are nonsyndromic (70%), 20% of which follow autosomal dominant mode of inheritance. Waardenburg syndrome (WS) ranks first among autosomal dominant syndromic forms of HI. WS is characterized by sensorineural hearing impairment, pigmentation abnormalities of hair and skin and hypoplastic blue eyes or heterochromia iridis. WS is subdivided into four major types, WS1-WS4. WS1 is diagnosed by the presence of dystopia canthorum and PAX3 is the only gene involved. This study aims to determine the pathogenic mutation in a large Iranian pedigree affected with WS1 in order to further confirm the clinical diagnosis. In the present study, a family segregating HI was ascertained in a genetic counseling center. Upon clinical inspection, white forelock, dystopia canthorum, broad high nasal root and synophrys, characteristic of WS1 were evident. In order to clarify the genetic etiology and confirm the clinical data, primers were designed to amplify exons and exon-intron boundaries of the responsible gene, PAX3 with 10 exons, followed by the Sanger DNA sequencing method. Genetic analysis of PAX3 revealed a novel mutation in PAX3 (c.1024_1040 del AGCACGATTCCTTCCAA). Our data provide genotype-phenotype correlation for the mutation in PAX3 and WS1 in the studied family, with implications for genetic counseling, which necessitates detailed clinical inspection of HI patients to distinguish syndromic HI from the more common non-syndromic cases. Our results reveal the value of phenotype-directed genetic analysis and could further expand the spectrum of PAX3 mutations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Clinical classification and genetic mutation study of two pedigrees with type II Waardenburg syndrome].

PubMed

Chen, Yong; Yang, Fuwei; Zheng, Hexin; Zhu, Ganghua; Hu, Peng; Wu, Weijing

2015-12-01

To explore the molecular etiology of two pedigrees affected with type II Waardenburg syndrome (WS2) and to provide genetic diagnosis and counseling. Blood samples were collected from the proband and his family members. Following extraction of genomic DNA, the coding sequences of PAX3, MITF, SOX10 and SNAI2 genes were amplified with PCR and subjected to DNA sequencing to detect potential mutations. A heterozygous deletional mutation c.649_651delAGA in exon 7 of the MITF gene has been identified in all patients from the first family, while no mutation was found in the other WS2 related genes including PAX3, MITF, SOX10 and SNAI2. The heterozygous deletion mutation c.649_651delAGA in exon 7 of the MITF gene probably underlies the disease in the first family. It is expected that other genes may also underlie WS2.

Waardenburg syndrome.

PubMed

Tagra, Sunita; Talwar, Amrita Kaur; Walia, Rattan Lal Singh; Sidhu, Puneet

2006-01-01

Waardenburg syndrome is a rare inherited and genetically heterogenous disorder of neural crest cell development. Four distinct subtypes showing marked interfamilial and intrafamilial variability have been described. We report a girl showing constellation of congenital hearing impairment with 110 dB and 105 dB loss in right and left ear respectively, hypoplastic blue iridis, white forelock, dystopia canthorum and broad nasal root. Other affected relatives of the family, with variable features of the syndrome, have been depicted in the pedigree.

Creation of miniature pig model of human Waardenburg syndrome type 2A by ENU mutagenesis.

PubMed

Hai, Tang; Guo, Weiwei; Yao, Jing; Cao, Chunwei; Luo, Ailing; Qi, Meng; Wang, Xianlong; Wang, Xiao; Huang, Jiaojiao; Zhang, Ying; Zhang, Hongyong; Wang, Dayu; Shang, Haitao; Hong, Qianlong; Zhang, Rui; Jia, Qitao; Zheng, Qiantao; Qin, Guosong; Li, Yongshun; Zhang, Tao; Jin, Weiwu; Chen, Zheng-Yi; Wang, Hongmei; Zhou, Qi; Meng, Anming; Wei, Hong; Yang, Shiming; Zhao, Jianguo

2017-11-01

Human Waardenburg syndrome 2A (WS2A) is a dominant hearing loss (HL) syndrome caused by mutations in the microphthalmia-associated transcription factor (MITF) gene. In mouse models with MITF mutations, WS2A is transmitted in a recessive pattern, which limits the study of hearing loss (HL) pathology. In the current study, we performed ENU (ethylnitrosourea) mutagenesis that resulted in substituting a conserved lysine with a serine (p. L247S) in the DNA-binding domain of the MITF gene to generate a novel miniature pig model of WS2A. The heterozygous mutant pig (MITF +/L247S ) exhibits a dominant form of profound HL and hypopigmentation in skin, hair, and iris, accompanied by degeneration of stria vascularis (SV), fused hair cells, and the absence of endocochlear potential, which indicate the pathology of human WS2A. Besides hypopigmentation and bilateral HL, the homozygous mutant pig (MITF L247S/L247S ) and CRISPR/Cas9-mediated MITF bi-allelic knockout pigs both exhibited anophthalmia. Three WS2 patients carrying MITF mutations adjacent to the corresponding region were also identified. The pig models resemble the clinical symptom and molecular pathology of human WS2A patients perfectly, which will provide new clues for better understanding the etiology and development of novel treatment strategies for human HL.

SOX10 mutation causes Waardenburg syndrome associated with distinctive phenotypic features in an Iranian family: A clue for phenotype-directed genetic analysis.

PubMed

Jalilian, Nazanin; Tabatabaiefar, Mohammad Amin; Alimadadi, Hossein; Noori-Daloii, Mohammad Reza

2017-05-01

Waardenburg syndrome (WS) is a neurocristopathy characterized by hearing impairment and pigmentary disturbances in hair, eyes, and skin. WS is clinically heterogeneous and can be subdivided into four major types (WS1-WS4) where WS4 or Shah-Waardenburg is diagnosed when WS2 is accompanied by Hirschsprung disease (HD). Mutations of SOX10, EDN3/EDNRB have been identified in association with WS4. This study was aimed to determine the pathogenic variant in an Iranian pedigree affected with WS4. A two-generation pedigree with three affected members and considerable phenotypic heterogeneity was recruited. The proband was a 15-year-old boy, with severe to profound sensorineural hearing impairment, heterochromia iridis, hypoplastic blue eyes and Hirschprung disease. The other two also presented characteristics of WS2 and complained of chronic constipation with normal anorectal reflex. Sequencing of all exons and exon-intron boundaries of SOX10, EDN3/EDNRB revealed a heterozygous variant c.422T > C in exon 3 of SOX10 confirmed by a series of evidence to be pathogenic. It resulted in p.L141P at the protein level. Leucin 141 is located in Nuclear Export signal, HMG box of the protein. This study is the first report of a WS4 family in the Iranian population. The mutation is associated with distinctive phenotypic profile (association of anosmia and chronic constipation with SOX10 mutations) and could further improve diagnosis and counseling of WS in the Iranian population and can contribute to phenotype-directed genetic analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional analysis of a nonstop mutation in MITF gene identified in a patient with Waardenburg syndrome type 2

PubMed Central

Sun, Jie; Hao, Ziqi; Luo, Hunjin; He, Chufeng; Mei, Lingyun; Liu, Yalan; Wang, Xueping; Niu, Zhijie; Chen, Hongsheng; Li, Jia-Da; Feng, Yong

2017-01-01

Waardenburg syndrome (WS) is an autosomal dominant inherited neurogenic disorder with the combination of various degrees of sensorineural deafness and pigmentary abnormalities affecting the skin, hair and eye. The four subtypes of WS were defined on the basis of the presence or absence of additional symptoms. Mutation of human microphthalmia-associated transcription factor (MITF) gene gives rise to WS2. Here, we identified a novel WS-associated mutation at the stop codon of MITF (p.X420Y) in a Chinese WS2 patient. This mutation resulted in an extension of extra 33 amino-acid residues in MITF. The mutant MITF appeared in both the nucleus and the cytoplasm, whereas the wild-type MITF was localized in the nucleus exclusively. The mutation led to a reduction in the transcriptional activities, whereas the DNA-binding activity was not altered. We show that the foremost mechanism was haploinsufficiency for the mild phenotypes of WS2 induced in X420Y MITF. PMID:28356565

Functional analysis of a nonstop mutation in MITF gene identified in a patient with Waardenburg syndrome type 2.

PubMed

Sun, Jie; Hao, Ziqi; Luo, Hunjin; He, Chufeng; Mei, Lingyun; Liu, Yalan; Wang, Xueping; Niu, Zhijie; Chen, Hongsheng; Li, Jia-Da; Feng, Yong

2017-07-01

Waardenburg syndrome (WS) is an autosomal dominant inherited neurogenic disorder with the combination of various degrees of sensorineural deafness and pigmentary abnormalities affecting the skin, hair and eye. The four subtypes of WS were defined on the basis of the presence or absence of additional symptoms. Mutation of human microphthalmia-associated transcription factor (MITF) gene gives rise to WS2. Here, we identified a novel WS-associated mutation at the stop codon of MITF (p.X420Y) in a Chinese WS2 patient. This mutation resulted in an extension of extra 33 amino-acid residues in MITF. The mutant MITF appeared in both the nucleus and the cytoplasm, whereas the wild-type MITF was localized in the nucleus exclusively. The mutation led to a reduction in the transcriptional activities, whereas the DNA-binding activity was not altered. We show that the foremost mechanism was haploinsufficiency for the mild phenotypes of WS2 induced in X420Y MITF.

Germinal mosaicism of PAX3 mutation caused Waardenburg syndrome type I.

PubMed

Chen, Kaitian; Zhan, Yuan; Wu, Xuan; Zong, Ling; Jiang, Hongyan

2018-01-01

Waardenburg syndrome mutations are most often recurrent or de novo. The rate of familial recurrence is low and families with several affected children are extremely rare. In this study, we aimed to clarify the underlying hereditary cause of Waardenburg syndrome type I in two siblings in a Chinese family, with a mother affected by prelingual mild hearing loss and a father who was negative for clinical symptoms of Waardenburg syndrome and had a normal hearing threshold. Complete characteristic features of the family members were recorded and genetic sequencing and parent-child relationship analyses were performed. The two probands were found to share double mutations in the PAX3/GJB2 genes that caused concurrent hearing loss in Waardenburg syndrome type I. Their mother carried the GJB2 c.109G > A homozygous mutation; however, neither the novel PAX3 c.592delG mutation, nor the Waardenburg syndrome phenotype, was observed in either parent. These previously unreported digenic mutations in PAX3/GJB2 resulted in deafness associated with Waardenburg syndrome type I in this family. To our knowledge, this is the first report describing germinal mosaicism in Waardenburg syndrome. This concept is important because it complicates genetic counseling of this family regarding the risk of recurrence of the mutations in subsequent pregnancies. Copyright © 2017 Elsevier B.V. All rights reserved.

Case report: waardenburg syndrome.

PubMed

Dumayas, Grace Lea; Capó-Aponte, José E

2015-03-01

A case of Waardenburg syndrome type 1 is described and relevant literature is reviewed to raise awareness about this rare syndrome, including the classification of each subtype and the differentiating clinical manifestations. A 44-year-old African-American female presented for a routine evaluation with hearing loss, dystopia canthorum (W index = 2.74), and almost complete gray hair. In addition, she presented with heterochromia irides, different fundus pigmentation between eyes. The patient did not have any upper limbs defect, cranial skeletal abnormalities, or intestinal disorders. Facial abnormalities and a white forelock are prominent features difficult to overlook during a routine ophthalmological examination. A careful medical history in patients with suspected Waardenburg syndrome is important to accurately classify this rare condition and to identify potential systemic implications associated to each subtype. The associated systemic complications can be addressed and managed through referral to the appropriate subspecialties. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Novel nonsense mutation of the endothelin-B receptor gene in a family with Waardenburg-Hirschsprung disease.

PubMed

Syrris, P; Carter, N D; Patton, M A

1999-11-05

Waardenburg syndrome (WS) comprises sensorineural hearing loss, hypopigmentation of skin and hair, and pigmentary disturbances of the irides. Four types of WS have been classified to date; in WS type IV (WS4), patients additionally have colonic aganglionosis (Hirschsprung disease, HSCR). Mutations in the endothelin-3 (EDN3), endothelin-B receptor (EDNRB), and Sox10 genes have been identified as causative for WS type IV. We screened a family with a combined WS-HSCR phenotype for mutations in the EDNRB locus using standard DNA mutation analysis and sequencing techniques. We have identified a novel nonsense mutation at codon 253 (CGA-->TGA, Arg-->STOP). This mutation leads to a premature end of the translation of EDNRB at exon 3, and it is predicted to produce a truncated and nonfunctional endothelin-B receptor. All affected relatives were heterozygous for the Arg(253)-->STOP mutation, whereas it was not observed in over 50 unrelated individuals used as controls. These data confirm the role of EDNRB in the cause of the Waardenburg-Hirschsprung syndrome and demonstrate that in WS-HSCR there is a lack of correlation between phenotype and genotype and a variable expression of disease even within the same family. Copyright 1999 Wiley-Liss, Inc.

A vestibular phenotype for Waardenburg syndrome?

NASA Technical Reports Server (NTRS)

Black, F. O.; Pesznecker, S. C.; Allen, K.; Gianna, C.

2001-01-01

OBJECTIVE: To investigate vestibular abnormalities in subjects with Waardenburg syndrome. STUDY DESIGN: Retrospective record review. SETTING: Tertiary referral neurotology clinic. SUBJECTS: Twenty-two adult white subjects with clinical diagnosis of Waardenburg syndrome (10 type I and 12 type II). INTERVENTIONS: Evaluation for Waardenburg phenotype, history of vestibular and auditory symptoms, tests of vestibular and auditory function. MAIN OUTCOME MEASURES: Results of phenotyping, results of vestibular and auditory symptom review (history), results of vestibular and auditory function testing. RESULTS: Seventeen subjects were women, and 5 were men. Their ages ranged from 21 to 58 years (mean, 38 years). Sixteen of the 22 subjects sought treatment for vertigo, dizziness, or imbalance. For subjects with vestibular symptoms, the results of vestibuloocular tests (calorics, vestibular autorotation, and/or pseudorandom rotation) were abnormal in 77%, and the results of vestibulospinal function tests (computerized dynamic posturography, EquiTest) were abnormal in 57%, but there were no specific patterns of abnormality. Six had objective sensorineural hearing loss. Thirteen had an elevated summating/action potential (>0.40) on electrocochleography. All subjects except those with severe hearing loss (n = 3) had normal auditory brainstem response results. CONCLUSION: Patients with Waardenburg syndrome may experience primarily vestibular symptoms without hearing loss. Electrocochleography and vestibular function tests appear to be the most sensitive measures of otologic abnormalities in such patients.

Genetic analysis of PAX3 for diagnosis of Waardenburg syndrome type I.

PubMed

Matsunaga, Tatsuo; Mutai, Hideki; Namba, Kazunori; Morita, Noriko; Masuda, Sawako

2013-04-01

PAX3 genetic analysis increased the diagnostic accuracy for Waardenburg syndrome type I (WS1). Analysis of the three-dimensional (3D) structure of PAX3 helped verify the pathogenicity of a missense mutation, and multiple ligation-dependent probe amplification (MLPA) analysis of PAX3 increased the sensitivity of genetic diagnosis in patients with WS1. Clinical diagnosis of WS1 is often difficult in individual patients with isolated, mild, or non-specific symptoms. The objective of the present study was to facilitate the accurate diagnosis of WS1 through genetic analysis of PAX3 and to expand the spectrum of known PAX3 mutations. In two Japanese families with WS1, we conducted a clinical evaluation of symptoms and genetic analysis, which involved direct sequencing, MLPA analysis, quantitative PCR of PAX3, and analysis of the predicted 3D structure of PAX3. The normal-hearing control group comprised 92 subjects who had normal hearing according to pure tone audiometry. In one family, direct sequencing of PAX3 identified a heterozygous mutation, p.I59F. Analysis of PAX3 3D structures indicated that this mutation distorted the DNA-binding site of PAX3. In the other family, MLPA analysis and subsequent quantitative PCR detected a large, heterozygous deletion spanning 1759-2554 kb that eliminated 12-18 genes including a whole PAX3 gene.

Novel mutations of endothelin-B receptor gene in Pakistani patients with Waardenburg syndrome.

PubMed

Jabeen, Raheela; Babar, Masroor Ellahi; Ahmad, Jamil; Awan, Ali Raza

2012-01-01

Mutations in EDNRB gene have been reported to cause Waardenburg-Shah syndrome (WS4) in humans. We investigated 17 patients with WS4 for identification of mutations in EDNRB gene using PCR and direct sequencing technique. Four genomic mutations were detected in four patients; a G to C transversion in codon 335 (S335C) in exon 5 and a transition of T to C in codon (S361L) in exon 5, a transition of A to G in codon 277 (L277L) in exon 4, a non coding transversion of T to A at -30 nucleotide position of exon 5. None of these mutations were found in controls. One of the patients harbored two novel mutations (S335C, S361L) in exon 5 and one in Intronic region (-30exon5 A>G). All of the mutations were homozygous and novel except the mutation observed in exon 4. In this study, we have identified 3 novel mutations in EDNRB gene associated with WS4 in Pakistani patients.

Point mutation in the MITF gene causing Waardenburg syndrome type II in a three-generation Indian family.

PubMed

Lalwani, A K; Attaie, A; Randolph, F T; Deshmukh, D; Wang, C; Mhatre, A; Wilcox, E

1998-12-04

Waardenburg syndrome (WS) is an autosomal-dominant neural crest cell disorder phenotypically characterized by hearing impairment and disturbance of pigmentation. A presence of dystopia canthorum is indicative of WS type 1, caused by loss of function mutation in the PAX3 gene. In contrast, type 2 WS (WS2) is characterized by normally placed medial canthi and is genetically heterogeneous; mutations in MITF (microphthalmia associated transcription factor) associated with WS2 have been identified in some but not all affected families. Here, we report on a three-generation Indian family with a point mutation in the MITF gene causing WS2. This mutation, initially reported in a Northern European family, creates a stop codon in exon 7 and is predicted to result in a truncated protein lacking the HLH-Zip or Zip structure necessary for normal interaction with its target DNA motif. Comparison of the phenotype between the two families demonstrates a significant difference in pigmentary disturbance of the eye. This family, with the first documented case of two unrelated WS2 families harboring identical mutations, provides additional evidence for the importance of genetic background on the clinical phenotype.

Familial co-segregation of Coffin-Lowry syndrome inherited from the mother and autosomal dominant Waardenburg type IV syndrome due to deletion of EDNRB inherited from the father.

PubMed

Loupe, Jacob; Sampath, Srirangan; Lacassie, Yves

2014-10-01

We report an African-American family that was identified after the proposita was referred for diagnostic evaluation at 4½ months with a history of Hirschsprung and dysmorphic features typical of Waardenburg syndrome (WS). Family evaluation revealed that the father had heterochromidia irides and hypertelorism supporting the clinical diagnosis of WS; however, examination of the mother revealed characteristic facial and digital features of Coffin-Lowry syndrome (CLS). Molecular testing of the mother identified a novel 2 bp deletion (c.865_866delCA) in codon 289 of RPS6KA3 leading to a frame-shift and premature termination of translation 5 codons downstream (NM_004586.2:p.Gln289ValfsX5). This deletion also was identified in the proposita and her three sisters with a clinical suspicion of CLS, all of whom as carriers for this X-linked disorder had very subtle manifestations. The molecular confirmation of WS type 4 (Shah-Waardenburg; WS4) was not as straightforward. To evaluate WS types 1-4, multiple sequential molecular tests were requested, including Sanger sequencing of all exons, and deletion/duplication analysis using MLPA for PAX3, MITF, SOX10, EDN3 and EDNRB. Although sequencing did not identify any disease causing variants, MLPA identified a heterozygous deletion of the entire EDNRB in the father. This deletion was also found in the proposita and the oldest child. Since the heterozygous deletion was the only change identified in EDNRB, this family represents one of the few cases of an autosomal dominant inheritance of WS4 involving the endothelin pathway. Altogether, clinical evaluation of the family revealed one child to be positive for WS4 and two positive for CLS, while two children were positive for both diseases simultaneously (including the proposita) while another pair test negative for either disease. This kinship is an example of the coincidence of two conditions co-segregating in one family, with variable phenotypes requiring molecular testing to

A zebrafish model for Waardenburg syndrome type IV reveals diverse roles for Sox10 in the otic vesicle.

PubMed

Dutton, Kirsten; Abbas, Leila; Spencer, Joanne; Brannon, Claire; Mowbray, Catriona; Nikaido, Masataka; Kelsh, Robert N; Whitfield, Tanya T

2009-01-01

In humans, mutations in the SOX10 gene are a cause of the auditory-pigmentary disorder Waardenburg syndrome type IV (WS4) and related variants. SOX10 encodes an Sry-related HMG box protein essential for the development of the neural crest; deafness in WS4 and other Waardenburg syndromes is usually attributed to loss of neural-crest-derived melanocytes in the stria vascularis of the cochlea. However, SOX10 is strongly expressed in the developing otic vesicle and so direct roles for SOX10 in the otic epithelium might also be important. Here, we examine the otic phenotype of zebrafish sox10 mutants, a model for WS4. As a cochlea is not present in the fish ear, the severe otic phenotype in these mutants cannot be attributed to effects on this tissue. In zebrafish sox10 mutants, we see abnormalities in all otic placodal derivatives. Gene expression studies indicate deregulated expression of several otic genes, including fgf8, in sox10 mutants. Using a combination of mutant and morphant data, we show that the three sox genes belonging to group E (sox9a, sox9b and sox10) provide a link between otic induction pathways and subsequent otic patterning: they act redundantly to maintain sox10 expression throughout otic tissue and to restrict fgf8 expression to anterior macula regions. Single-cell labelling experiments indicate a small and transient neural crest contribution to the zebrafish ear during normal development, but this is unlikely to account for the strong defects seen in the sox10 mutant. We discuss the implication that the deafness in WS4 patients with SOX10 mutations might reflect a haploinsufficiency for SOX10 in the otic epithelium, resulting in patterning and functional abnormalities in the inner ear.

Clinical manifestations of Waardenburg syndrome in a male adolescent in Mali, West Africa.

PubMed

Imperato, Pascal James; Imperato, Gavin H

2015-02-01

Waardenburg syndrome (WS) is a genetic disorder of which there are four distinct types. These four types are differentiated by the physical defects which they produce. Presented here is the case of a 13-year-old boy with WS Type I who was observed and physically assessed in Mali, West Africa in 1969. His physical findings included a bright blue coloring to the irises of the eyes, profound sensorineural deafness, mutism, dystopia canthorum (lateral displacement of the inner canthi of the eyes), broad nasal root, bushy eyebrows, and scaphoid deformities of the supraorbital portions of the frontal bone. Because family members were not available for interviews or physical examinations, it was not possible to determine if this patient was suffering from a congenital form of the disorder or from a spontaneous mutation. Given the patient's then location in a remote rural area of Mali where electricity was absent, it was not possible to perform additional diagnostic tests. The patient described here is the first with WS in Mali, West Africa to have been medically observed and evaluated and later documented in the medical literature. A second case of the syndrome in Mali was described in the medical literature in 2011 in an 18-month-old infant who did not have sensorineural hearing loss, but who did have a bilateral cleft lip. An historical overview of WS is presented along with details concerning the characteristics of the four types of the disorder.

Inner ear anatomy in Waardenburg syndrome: radiological assessment and comparison with normative data.

PubMed

Kontorinis, Georgios; Goetz, Friedrich; Lanfermann, Heinrich; Luytenski, Stefan; Giesemann, Anja M

2014-08-01

As patients with Waardenburg syndrome (WS) represent potential candidates for cochlear implantation, their inner ear anatomy is of high significance. There is an ongoing debate whether WS is related to any inner ear dysplasias. Our objective was to evaluate radiologically the inner ear anatomy in patients with WS and identify any temporal bone malformations. A retrospective case review was carried out in a tertiary, referral center. The high resolution computed tomography (HRCT) scans of the temporal bone from 20 patients (40 ears) with WS who were managed for deafness in a tertiary referral center from 1995 to 2012 were retrospectively examined. Measurements of 15 different inner ear dimensions, involving the cochlea, the vestibule, the semicircular canals and the internal auditory meatus, as well as measurements of the vestibular aqueduct, were performed independently by two neuroradiologists. Finally, we compared the results from the WS group with a control group consisting of 50 normal hearing subjects (100 ears) and with previously reported normative values. Inner ear malformations were not found in any of the patients with WS. All measured inner ear dimensions were within the normative values compiled by our study group as well as by others. Inner ear malformations are not characteristic for all types of WS; however, certain rare subtypes might be related to inner ear deformities. Normative cochleovestibular dimensions that can help in assessing the temporal bone anatomy are provided. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Novel mutations in the SOX10 gene in the first two Chinese cases of type IV Waardenburg syndrome.

PubMed

Jiang, Lu; Chen, Hongsheng; Jiang, Wen; Hu, Zhengmao; Mei, Lingyun; Xue, Jingjie; He, Chufeng; Liu, Yalan; Xia, Kun; Feng, Yong

2011-05-20

We analyzed the clinical features and family-related gene mutations for the first two Chinese cases of type IV Waardenburg syndrome (WS4). Two families were analyzed in this study. The analysis included a medical history, clinical analysis, a hearing test and a physical examination. In addition, the EDNRB, EDN3 and SOX10 genes were sequenced in order to identify the pathogenic mutation responsible for the WS4 observed in these patients. The two WS4 cases presented with high phenotypic variability. Two novel heterozygous mutations (c.254G>A and c.698-2A>T) in the SOX10 gene were detected. The mutations identified in the patients were not found in unaffected family members or in 200 unrelated control subjects. This is the first report of WS4 in Chinese patients. In addition, two novel mutations in SOX10 gene have been identified. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Audiological outcomes of cochlear implantation in Waardenburg Syndrome

PubMed Central

Magalhães, Ana Tereza de Matos; Samuel, Paola Angélica; Goffi-Gomez, Maria Valeria Schimdt; Tsuji, Robinson Koji; Brito, Rubens; Bento, Ricardo Ferreira

2013-01-01

Summary Introduction: The most relevant clinical symptom in Waardenburg syndrome is profound bilateral sensorioneural hearing loss. Aim: To characterize and describe hearing outcomes after cochlear implantation in patients with Waardenburg syndrome to improve preoperative expectations. Method: This was an observational and retrospective study of a series of cases. Children who were diagnosed with Waardenburg syndrome and who received a multichannel cochlear implant between March 1999 and July 2012 were included in the study. Intraoperative neural response telemetry, hearing evaluation, speech perception, and speech production data before and after surgery were assessed. Results: During this period, 806 patients received a cochlear implant and 10 of these (1.2%) were diagnosed with Waardenburg syndrome. Eight of the children received a Nucleus 24® implant and 1 child and 1 adult received a DigiSonic SP implant. The mean age at implantation was 44 months among the children. The average duration of use of a cochlear implant at the time of the study was 43 months. Intraoperative neural responses were present in all cases. Patients who could use the speech processor effectively had a pure tone average of 31 dB in free-field conditions. In addition, the MUSS and MAIS questionnaires revealed improvements in speech perception and production. Four patients did not have a good outcome, which might have been associated with ineffective use of the speech processor. Conclusion: Despite the heterogeneity of the group, patients with Waardenburg syndrome who received cochlear implants were found to have hearing thresholds that allowed access to speech sounds. However, patients who received early intervention and rehabilitation showed better evolution of auditory perception. PMID:25992025

Audiological outcomes of cochlear implantation in Waardenburg Syndrome.

PubMed

Magalhães, Ana Tereza de Matos; Samuel, Paola Angélica; Goffi-Gomez, Maria Valeria Schimdt; Tsuji, Robinson Koji; Brito, Rubens; Bento, Ricardo Ferreira

2013-07-01

 The most relevant clinical symptom in Waardenburg syndrome is profound bilateral sensorioneural hearing loss.  To characterize and describe hearing outcomes after cochlear implantation in patients with Waardenburg syndrome to improve preoperative expectations.  This was an observational and retrospective study of a series of cases. Children who were diagnosed with Waardenburg syndrome and who received a multichannel cochlear implant between March 1999 and July 2012 were included in the study. Intraoperative neural response telemetry, hearing evaluation, speech perception, and speech production data before and after surgery were assessed.  During this period, 806 patients received a cochlear implant and 10 of these (1.2%) were diagnosed with Waardenburg syndrome. Eight of the children received a Nucleus 24(®) implant and 1 child and 1 adult received a DigiSonic SP implant. The mean age at implantation was 44 months among the children. The average duration of use of a cochlear implant at the time of the study was 43 months. Intraoperative neural responses were present in all cases. Patients who could use the speech processor effectively had a pure tone average of 31 dB in free-field conditions. In addition, the MUSS and MAIS questionnaires revealed improvements in speech perception and production. Four patients did not have a good outcome, which might have been associated with ineffective use of the speech processor.  Despite the heterogeneity of the group, patients with Waardenburg syndrome who received cochlear implants were found to have hearing thresholds that allowed access to speech sounds. However, patients who received early intervention and rehabilitation showed better evolution of auditory perception.

CHOROIDAL MELANOMA IN A PATIENT WITH WAARDENBURG SYNDROME.

PubMed

Itty, Sujit; Richter, Elizabeth R; McCannel, Tara A

2015-01-01

To report a case of choroidal malignant melanoma in a patient with Waardenburg syndrome and bilateral choroidal pigmentary abnormalities. Clinical examination and multimodal imaging of the case. A 45-year-old woman presented with asymptomatic flat choroidal pigmentation abnormalities in both eyes. A choroidal lesion was identified in the inferotemporal periphery of the left eye arising from an area of hyperpigmentation; ultrasonography findings were consistent with a choroidal melanoma. The patient endorsed a personal and family history of premature graying of hair and was identified to have dystopia canthorum consistent with the diagnosis of Waardenburg syndrome. The authors present the first reported case of concurrent Waardenburg syndrome and choroidal malignant melanoma. This cooccurrence may suggest that the relative hyperpigmented regions in affected fundi may be abnormal and should be monitored closely for the development of choroidal melanoma.

A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome).

PubMed

Hofstra, R M; Osinga, J; Tan-Sindhunata, G; Wu, Y; Kamsteeg, E J; Stulp, R P; van Ravenswaaij-Arts, C; Majoor-Krakauer, D; Angrist, M; Chakravarti, A; Meijers, C; Buys, C H

1996-04-01

Hirschsprung disease (HSCR) or colonic aganglionosis is a congenital disorder characterized by an absence of intramural ganglia along variable lengths of the colon resulting in intestinal obstruction. The incidence of HSCR is 1 in 5,000 live births. Mutations in the RET gene, which codes for a receptor tyrosine kinase, and in EDNRB which codes for the endothelin-B receptor, have been shown to be associated with HSCR in humans. The lethal-spotted mouse which has pigment abnormalities, but also colonic aganglionosis, carries a mutation in the gene coding for endothelin 3 (Edn3), the ligand for the receptor protein encoded by EDNRB. Here, we describe a mutation of the human gene for endothelin 3 (EDN3), homozygously present in a patient with a combined Waardenburg syndrome type 2 (WS2) and HSCR phenotype (Shah-Waardenburg syndrome). The mutation, Cys159Phe, in exon 3 in the ET-3 like domain of EDN3, presumably affects the proteolytic processing of the preproendothelin to the mature peptide EDN3. The patient's parents were first cousins. A previous child in this family had been diagnosed with a similar combination of HSCR, depigmentation and deafness. Depigmentation and deafness were present in other relatives. Moreover, we present a further indication for the involvement of EDNRB in HSCR by reporting a novel mutation detected in one of 40 unselected HSCR patients.

[PAX3 gene mutation analysis for two Waardenburg syndrome type Ⅰ families and their prenatal diagnosis].

PubMed

Bai, Y; Liu, N; Kong, X D; Yan, J; Qin, Z B; Wang, B

2016-12-07

Objective: To analyze the mutations of PAX3 gene in two Waardenburg syndrome type Ⅰ (WS1) pedigrees and make prenatal diagnosis for the high-risk 18-week-old fetus. Methods: PAX3 gene was first analyzed by Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA) for detecting pathogenic mutation of the probands of the two pedigrees. The mutations were confirmed by MLPA and Sanger in parents and unrelated healthy individuals.Prenatal genetic diagnosis for the high-risk fetus was performed by amniotic fluid cell after genotyping. Results: A heterozygous PAX3 gene gross deletion (E7 deletion) was identified in all patients from WS1-01 family, and not found in 20 healthy individuals.Prenatal diagnosis in WS1-01 family indicated that the fetus was normal. Molecular studies identified a novel deletion mutation c. 1385_1386delCT within the PAX3 gene in all affected WS1-02 family members, but in none of the unaffected relatives and 200 healthy individuals. Conclusions: PAX3 gene mutation is etiological for two WS1 families. Sanger sequencing plus MLPA is effective and accurate for making gene diagnosis and prenatal diagnosis.

Anaesthesia Management in a Patient with Waardenburg Syndrome and Review of the Literature.

PubMed

Peker, Kevser; Ergil, Julide; Öztürk, İbrahim

2015-10-01

Waardenburg syndrome is a rare autosomal dominant disease that may cause hearing loss, pigmentary abnormalities, neurocristopathy and partial albinism. Incidence is estimated as 2%-3% among the cases of congenital deafness and 1/42,000 of the general population. Children with Waardenburg syndrome usually require anaesthesia for the cochlear implant operation in early age. The features of the syndrome that may bear importance for anaesthetic management are laryngomalacia, multiple muscle contractures, limited neck movements, cyanotic cardiopathy and electrolyte imbalance. Patients with Waardenburg syndrome stand for difficult airway. We aimed to report anaesthetic management of a child with Waardenburg syndrome who underwent surgery for cochlear implantation.

Anaesthesia Management in a Patient with Waardenburg Syndrome and Review of the Literature

PubMed Central

Peker, Kevser; Ergil, Julide; Öztürk, İbrahim

2015-01-01

Waardenburg syndrome is a rare autosomal dominant disease that may cause hearing loss, pigmentary abnormalities, neurocristopathy and partial albinism. Incidence is estimated as 2%–3% among the cases of congenital deafness and 1/42,000 of the general population. Children with Waardenburg syndrome usually require anaesthesia for the cochlear implant operation in early age. The features of the syndrome that may bear importance for anaesthetic management are laryngomalacia, multiple muscle contractures, limited neck movements, cyanotic cardiopathy and electrolyte imbalance. Patients with Waardenburg syndrome stand for difficult airway. We aimed to report anaesthetic management of a child with Waardenburg syndrome who underwent surgery for cochlear implantation. PMID:27366529

Waardenberg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: First report of the WS consortium

PubMed Central

Farrer, Lindsay A.; Grundfast, Kenneth M.; Amos, Jean; Arnos, Kathleen S.; Asher, James H.; Beighton, Peter; Diehl, Scott R.; Fex, Jörgen; Foy, Carole; Friedman, Thomas B.; Greenberg, Jacquie; Hoth, Christopher; Marazita, Mary; Milunsky, Aubrey; Morell, Robert; Nance, Walter; Newton, Valerie; Ramesar, Rajkumar; Agustin, Theresa B. San; Skare, James; Stevens, Cathy A.; Wagner, Ronald G.; Wilcox, Edward R.; Winship, Ingrid; Read, Andrew P.

1992-01-01

Previous studies have localized the gene for Waardenburg syndrome (WS) type I to the distal portion of chromosome 2q, near the ALPP locus. We pooled linkage data obtained from 41 WS type I and 3 WS type II families which were typed for six polymorphic loci on chromosome 2q in order to refine the location of the WS locus (WS1) and evaluate the extent of genetic heterogeneity. In the course of this work, we developed diagnostic criteria for genetic and phenotypic studies. Our findings, based on two-locus and multilocus analysis using a linkage map established from reference pedigrees, suggest that there are two or more mutations causing WS, one of which (i.e., WS1) is located on chromosome 2q, between the ALPP and FN1 loci, at distances of 7.8 cM and 11.2 cM for each marker, respectively. The results also indicate that WS1 is responsible for the illness in approximately 45% of all families in this sample. However, the odds favoring this position over a location between ALPP and SAG are only 2:1 when alternate assumptions about the proportion of linked families are considered. We conclude that a more saturated map of this region of chromosome 2q, including highly polymorphic markers, will be needed to accurately distinguish linked families and, ultimately, isolate the mutant gene. PMID:1349198

A novel mutation of the MITF gene in a family with Waardenburg syndrome type 2: A case report

PubMed Central

SHI, YUNFANG; LI, XIAOZHOU; JU, DUAN; LI, YAN; ZHANG, XIULING; ZHANG, YING

2016-01-01

Waardenburg syndrome (WS) is an autosomal dominant disorder with varying degrees of sensorineural hearing loss, and accumulation of pigmentation in hair, skin and iris. There are four types of WS (WS1–4) with differing characteristics. Mutations in six genes [paired box gene 3 (PAX3), microphthalmia-associated transcription factor (MITF), endothelin 3 (END3), endothelin receptor type B (EDNRB), SRY (sex determining region Y)-box 10 (SOX10) and snail homolog 2 (SNAI2)] have been identified to be associated with the various types. This case report describes the investigation of genetic mutations in three patients with WS2 from a single family. Genomic DNA was extracted, and the six WS-related genes were sequenced using next-generation sequencing technology. In addition to mutations in PAX3, EDNRB and SOX10, a novel heterozygous MITF mutation, p.Δ315Arg (c.944_946delGAA) on exon 8 was identified. This is predicted to be a candidate disease-causing mutation that may affect the structure and function of the enzyme. PMID:27073475

A novel mutation of the MITF gene in a family with Waardenburg syndrome type 2: A case report.

PubMed

Shi, Yunfang; Li, Xiaozhou; Ju, Duan; Li, Yan; Zhang, Xiuling; Zhang, Ying

2016-04-01

Waardenburg syndrome (WS) is an autosomal dominant disorder with varying degrees of sensorineural hearing loss, and accumulation of pigmentation in hair, skin and iris. There are four types of WS (WS1-4) with differing characteristics. Mutations in six genes [paired box gene 3 ( PAX3 ), microphthalmia-associated transcription factor ( MITF ), endothelin 3 ( END3 ), endothelin receptor type B ( EDNRB ), SRY (sex determining region Y)-box 10 ( SOX10 ) and snail homolog 2 ( SNAI2 )] have been identified to be associated with the various types. This case report describes the investigation of genetic mutations in three patients with WS2 from a single family. Genomic DNA was extracted, and the six WS-related genes were sequenced using next-generation sequencing technology. In addition to mutations in PAX3, EDNRB and SOX10, a novel heterozygous MITF mutation, p.Δ315Arg (c.944_946delGAA) on exon 8 was identified. This is predicted to be a candidate disease-causing mutation that may affect the structure and function of the enzyme.

Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family.

PubMed

Sólia-Nasser, L; de Aquino, S-N; Paranaíba, L-M R; Gomes, A; Dos-Santos-Neto, P; Coletta, R-D; Cardoso, A-F; Frota, A-C; Martelli-Júnior, H

2016-05-01

The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1.

[SOX10 mutation is relevant to inner ear malformation in patients with Waardenburg syndrome].

PubMed

Xu, G Y; Hao, Q Q; Zhong, L L; Ren, W; Yan, Y; Liu, R Y; Li, J N; Guo, W W; Zhao, H; Yang, S M

2016-11-07

Objective: To determine the relevance between the SOX 10 mutation and Waardenburg syndrome (WS) accompanied with inner ear abnormality by analyzing the inner ear imaging results and molecular and genetic results of the WS patients with the SOX 10 mutation. Methods: This study included 36 WS in patients during 2001 and 2015 in the department of otorhinolaryngology head and neck surgery, Chinese Peoples's Liberation Army General Hospital. The condition of the inner ear of each patient was assessed by analyzing HRCT scans of the temporal bone and MRI scans of the brain and internal auditory canal. Meanwhile, the possible pathogenic genes of WS, including SOX10, MITF , and PAX 3, were also screened. Patients were divided into two groups according to SOX 10 mutation.The Fisher accuracy test was used to determine statistical difference of inner ear deformation incidence between the two groups. Results: Among all 36 patients, 12 were found to have inner ear abnormality. Most abnormalities were posterior semicircular canal deformations, some accompanied with cochlear deformation and an enlarged vestibule. Among all patients, 9 patients were SOX 10 heterozygous mutation carriers, among which six showed bilateral inner ear abnormality. Fisher accuracy test results suggested a significant correlation between the SOX 10 mutation and inner ear abnormality in WS patients ( P =0.036). Conclusion: This study found that WS patients with the SOX 10 mutation are more likely to have deformed inner ears when compared to WS patients without the SOX 10 mutation.

Waardenburg Syndrome: An Unusual Indication of Cochlear Implantation Experienced in 11 Patients.

PubMed

Bayrak, Feda; Çatlı, Tolgahan; Atsal, Görkem; Tokat, Taşkın; Olgun, Levent

2017-08-01

The aim of this study was to present the surgical findings of children with Waardenburg syndrome (WS) and investigate speech development after cochlear implantation in this unique group of patients. A retrospective chart review of the patients diagnosed with WS and implanted between 1998 and 2015 was performed. Categories of auditory performance (CAP) test were used to assess the auditory skills of these patients. CAP is a nonlinear hierarchical scale used to rate a child's developing auditory abilities. Preoperative test results and intraoperative surgical findings of these patients have been presented. In total, 1835 cases were implanted a tour institution, and 1210 of these were children. Among these implantees, 11 were diagnosed with WS (0.59% of all implantees). Four of the 11 patients showed incomplete partition type 2bony labyrinth abnormality (Mondini deformity) and all patients showed intraoperative gusher during cochleostomy, which was subsided through routine interventions. No other complications occurred during surgery, and all patients showed satisfactory CAP results in the late postoperative period. Our experiences with cochlear implantation in patients with WS showed that the procedure is safe and effective in this group of patients. Surgeons should be aware of possible labyrinth malformations and intraoperative problems such as gusher in these patients. In long term, auditory performances may exhibit satisfactory results with optimal postoperative educational and supportive measures.

Waardenburg Syndrome: A Case Study of Two Patients.

PubMed

Sharma, Karan; Arora, Archana

2015-09-01

Waardenburg syndrome is an autosomal dominant disorder with an incidence of 1 in 40,000 that manifests with sensorineural deafness, pigmentation defects of the skin, hair and iris and various defects of neural crest-derived tissues. This genetically heterogeneous disease accounts for >2 % of the congenitally deaf population. Mutations in the EDN3, EDNRB, MITF, PAX3, SNAI2, and SOX10 genes can cause Waardenburg syndrome. We here report a case of 12 year old female who presented with chief complaint of decreased hearing in both ears and had clinical features consistent with Waardenburg syndrome. She had a distinct white forelock of hair in the midline along with striking bilateral blue iris. Also a white depigmented patch was present on the right forearm. Both eyes had bright red fundal reflex with choroidal depigmentation. Her younger brother, the second case in this study, had similar blue eyes, white forelock of hair, depigmented skin patch and choroidal depigmentation but with normal hearing. Their father had a history of premature graying of hair. All the primary care physicians coming across a child with blue eyes and white forelock of hair should get the child's hearing tested at the first instance, if not already tested. An early diagnosis and improvement of hearing impairment with timely intervention are the most important for psychological and intellectual development of children with Waardenburg syndrome.

Waardenburg syndrome: Novel mutations in a large Brazilian sample.

PubMed

Bocángel, Magnolia Astrid Pretell; Melo, Uirá Souto; Alves, Leandro Ucela; Pardono, Eliete; Lourenço, Naila Cristina Vilaça; Marcolino, Humberto Vicente Cezar; Otto, Paulo Alberto; Mingroni-Netto, Regina Célia

2018-06-01

This paper deals with the molecular investigation of Waardenburg syndrome (WS) in a sample of 49 clinically diagnosed probands (most from southeastern Brazil), 24 of them having the type 1 (WS1) variant (10 familial and 14 isolated cases) and 25 being affected by the type 2 (WS2) variant (five familial and 20 isolated cases). Sequential Sanger sequencing of all coding exons of PAX3, MITF, EDN3, EDNRB, SOX10 and SNAI2 genes, followed by CNV detection by MLPA of PAX3, MITF and SOX10 genes in selected cases revealed many novel pathogenic variants. Molecular screening, performed in all patients, revealed 19 causative variants (19/49 = 38.8%), six of them being large whole-exon deletions detected by MLPA, seven (four missense and three nonsense substitutions) resulting from single nucleotide substitutions (SNV), and six representing small indels. A pair of dizygotic affected female twins presented the c.430delC variant in SOX10, but the mutation, imputed to gonadal mosaicism, was not found in their unaffected parents. At least 10 novel causative mutations, described in this paper, were found in this Brazilian sample. Copy-number-variation detected by MLPA identified the causative mutation in 12.2% of our cases, corresponding to 31.6% of all causative mutations. In the majority of cases, the deletions were sporadic, since they were not present in the parents of isolated cases. Our results, as a whole, reinforce the fact that the screening of copy-number-variants by MLPA is a powerful tool to identify the molecular cause in WS patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Waardenburg syndrome in four Mexican patients.

PubMed

Aguilar Caso, Sandra I; Ortiz Nieva, Gabriela

2009-01-01

Waardenburg syndrome is a hereditary auditory-pigmentary syndrome. The major features include pigmentary disturbances and congenital deafness. Clinical findings are extremely variable, not only at the authors' institution but also in the literature. The authors describe four patients who presented with various clinical features and different genetic pedigree penetration.

The Hearing Outcomes of Cochlear Implantation in Waardenburg Syndrome.

PubMed

Koyama, Hajime; Kashio, Akinori; Sakata, Aki; Tsutsumiuchi, Katsuhiro; Matsumoto, Yu; Karino, Shotaro; Kakigi, Akinobu; Iwasaki, Shinichi; Yamasoba, Tatsuya

2016-01-01

Objectives. This study aimed to determine the feasibility of cochlear implantation for sensorineural hearing loss in patients with Waardenburg syndrome. Method. A retrospective chart review was performed on patients who underwent cochlear implantation at the University of Tokyo Hospital. Clinical classification, genetic mutation, clinical course, preoperative hearing threshold, high-resolution computed tomography of the temporal bone, and postoperative hearing outcome were assessed. Result. Five children with Waardenburg syndrome underwent cochlear implantation. The average age at implantation was 2 years 11 months (ranging from 1 year 9 months to 6 years 3 months). Four patients had congenital profound hearing loss and one patient had progressive hearing loss. Two patients had an inner ear malformation of cochlear incomplete partition type 2. No surgical complication or difficulty was seen in any patient. All patients showed good hearing outcome postoperatively. Conclusion. Cochlear implantation could be a good treatment option for Waardenburg syndrome.

The Hearing Outcomes of Cochlear Implantation in Waardenburg Syndrome

PubMed Central

Koyama, Hajime; Kashio, Akinori; Sakata, Aki; Tsutsumiuchi, Katsuhiro; Matsumoto, Yu; Karino, Shotaro; Kakigi, Akinobu; Iwasaki, Shinichi; Yamasoba, Tatsuya

2016-01-01

Objectives. This study aimed to determine the feasibility of cochlear implantation for sensorineural hearing loss in patients with Waardenburg syndrome. Method. A retrospective chart review was performed on patients who underwent cochlear implantation at the University of Tokyo Hospital. Clinical classification, genetic mutation, clinical course, preoperative hearing threshold, high-resolution computed tomography of the temporal bone, and postoperative hearing outcome were assessed. Result. Five children with Waardenburg syndrome underwent cochlear implantation. The average age at implantation was 2 years 11 months (ranging from 1 year 9 months to 6 years 3 months). Four patients had congenital profound hearing loss and one patient had progressive hearing loss. Two patients had an inner ear malformation of cochlear incomplete partition type 2. No surgical complication or difficulty was seen in any patient. All patients showed good hearing outcome postoperatively. Conclusion. Cochlear implantation could be a good treatment option for Waardenburg syndrome. PMID:27376080

A gene for Waardenburg syndrome type 2 maps close to the human homologue of the microphthalmia gene at chromosome 3p12-p14.1.

PubMed

Hughes, A E; Newton, V E; Liu, X Z; Read, A P

1994-08-01

Waardenburg syndrome (WS), an autosomal dominant syndrome of hearing loss and pigmentary disturbances, comprises at least two separate conditions. WS type 1 is normally caused by mutations in PAX3 located at chromosome 2q35 and is distinguished clinically by minor facial malformations. We have now located a gene for WS type 2. Two families show linkage to a group of microsatellite markers located on chromosome 3p12-p14.1. D3S1261 gave a maximum lod score of 6.5 at zero recombination in one large Type 2 family. In a second, smaller family the adjacent marker D3S1210 gave a lod of 2.05 at zero recombination. Interestingly, the human homologue (MITF) of the mouse microphthalmia gene, a good candidate at the phenotypic level, has recently been mapped to 3p12.3-p14.4.

Molecular etiology and genotype-phenotype correlation of Chinese Han deaf patients with type I and type II Waardenburg Syndrome.

PubMed

Sun, Lianhua; Li, Xiaohua; Shi, Jun; Pang, Xiuhong; Hu, Yechen; Wang, Xiaowen; Wu, Hao; Yang, Tao

2016-10-19

Waardenburg syndrome (WS) characterized by sensorineural hearing loss and pigmentary abnormalities is genetically heterogeneous and phenotypically variable. This study investigated the molecular etiology and genotype-phenotype correlation of WS in 36 Chinese Han deaf probands and 16 additional family members that were clinically diagnosed with WS type I (WS1, n = 8) and type II (WS2, n = 42). Mutation screening of six WS-associated genes detected PAX3 mutations in 6 (86%) of the 7 WS1 probands. Among the 29 WS2 probands, 13 (45%) and 10 (34%) were identified with SOX10 and MITF mutations, respectively. Nineteen of the 26 detected mutations were novel. In WS2 probands whose parental DNA samples were available, de novo mutations were frequently seen for SOX10 mutations (7/8) but not for MITF mutations (0/5, P = 0.005). Excessive freckle, a common feature of WS2 in Chinese Hans, was frequent in WS2 probands with MITF mutations (7/10) but not in those with SOX10 mutations (0/13, P = 4.9 × 10 -4 ). Our results showed that mutations in SOX10 and MITF are two major causes for deafness associated with WS2. These two subtypes of WS2 can be distinguished by the high de novo rate of the SOX10 mutations and the excessive freckle phenotype exclusively associated with the MITF mutations.

Molecular etiology and genotype-phenotype correlation of Chinese Han deaf patients with type I and type II Waardenburg Syndrome

PubMed Central

Sun, Lianhua; Li, Xiaohua; Shi, Jun; Pang, Xiuhong; Hu, Yechen; Wang, Xiaowen; Wu, Hao; Yang, Tao

2016-01-01

Waardenburg syndrome (WS) characterized by sensorineural hearing loss and pigmentary abnormalities is genetically heterogeneous and phenotypically variable. This study investigated the molecular etiology and genotype-phenotype correlation of WS in 36 Chinese Han deaf probands and 16 additional family members that were clinically diagnosed with WS type I (WS1, n = 8) and type II (WS2, n = 42). Mutation screening of six WS-associated genes detected PAX3 mutations in 6 (86%) of the 7 WS1 probands. Among the 29 WS2 probands, 13 (45%) and 10 (34%) were identified with SOX10 and MITF mutations, respectively. Nineteen of the 26 detected mutations were novel. In WS2 probands whose parental DNA samples were available, de novo mutations were frequently seen for SOX10 mutations (7/8) but not for MITF mutations (0/5, P = 0.005). Excessive freckle, a common feature of WS2 in Chinese Hans, was frequent in WS2 probands with MITF mutations (7/10) but not in those with SOX10 mutations (0/13, P = 4.9 × 10−4). Our results showed that mutations in SOX10 and MITF are two major causes for deafness associated with WS2. These two subtypes of WS2 can be distinguished by the high de novo rate of the SOX10 mutations and the excessive freckle phenotype exclusively associated with the MITF mutations. PMID:27759048

[Clinical features of a Chinese pedigree with Waardenburg syndrome type 2].

PubMed

Yang, Shu-zhi; Yuan, Hui-jun; Bai, Lin-na; Cao, Ju-yang; Xu, Ye; Shen, Wei-dong; Ji, Fei; Yang, Wei-yan

2005-10-12

To investigate detailed clinical features of a Chinese pedigree with Waardenburg syndrome type 2. Members of this pedigree were interviewed to identify personal or family medical histories of hearing loss, the use of aminoglycosides, and other clinical abnormalities by filling questionnaire. The audiological and other clinical evaluations of the proband and other members of this family were conducted, including pure-tone audiometry, immittance and auditory brain-stem response and ophthalmological, dermatologic, hair, temporal bone CT examinations. This family is categorized as Waardenburg syndrome type 2 according to its clinical features. It's an autosomal dominant disorder with incomplete penetrance. The clinical features varied greatly among family members and characterized by sensorineural hearing loss, heterochromia irides, freckle on the face and premature gray hair. Hearing loss can be unilateral or bilateral, congenital or late onset in this family. This Chinese family has some unique clinical features comparing with the international diagnostic criteria for Waardenburg syndrome. This study may provide some evidences to amend the diagnostic criteria for Waardenburg syndrome in Chinese population.

Spectrum of novel mutations found in Waardenburg syndrome types 1 and 2: implications for molecular genetic diagnostics.

PubMed

Wildhardt, Gabriele; Zirn, Birgit; Graul-Neumann, Luitgard M; Wechtenbruch, Juliane; Suckfüll, Markus; Buske, Annegret; Bohring, Axel; Kubisch, Christian; Vogt, Stefanie; Strobl-Wildemann, Gertrud; Greally, Marie; Bartsch, Oliver; Steinberger, Daniela

2013-03-18

Till date, mutations in the genes PAX3 and MITF have been described in Waardenburg syndrome (WS), which is clinically characterised by congenital hearing loss and pigmentation anomalies. Our study intended to determine the frequency of mutations and deletions in these genes, to assess the clinical phenotype in detail and to identify rational priorities for molecular genetic diagnostics procedures. Prospective analysis. 19 Caucasian patients with typical features of WS underwent stepwise investigation of PAX3 and MITF. When point mutations and small insertions/deletions were excluded by direct sequencing, copy number analysis by multiplex ligation-dependent probe amplification was performed to detect larger deletions and duplications. Clinical data and photographs were collected to facilitate genotype-phenotype analyses. All analyses were performed in a large German laboratory specialised in genetic diagnostics. 15 novel and 4 previously published heterozygous mutations in PAX3 and MITF were identified. Of these, six were large deletions or duplications that were only detectable by copy number analysis. All patients with PAX3 mutations had typical phenotype of WS with dystopia canthorum (WS1), whereas patients with MITF gene mutations presented without dystopia canthorum (WS2). In addition, one patient with bilateral hearing loss and blue eyes with iris stroma dysplasia had a de novo missense mutation (p.Arg217Ile) in MITF. MITF 3-bp deletions at amino acid position 217 have previously been described in patients with Tietz syndrome (TS), a clinical entity with hearing loss and generalised hypopigmentation. On the basis of these findings, we conclude that sequencing and copy number analysis of both PAX3 and MITF have to be recommended in the routine molecular diagnostic setting for patients, WS1 and WS2. Furthermore, our genotype-phenotype analyses indicate that WS2 and TS correspond to a clinical spectrum that is influenced by MITF mutation type and position.

[Cochlear implantation in patients with Waardenburg syndrome type II].

PubMed

Wan, Liangcai; Guo, Menghe; Chen, Shuaijun; Liu, Shuangriu; Chen, Hao; Gong, Jian

2010-05-01

To describe the multi-channel cochlear implantation in patients with Waardenburg syndrome including surgeries, pre and postoperative hearing assessments as well as outcomes of speech recognition. Multi-channel cochlear implantation surgeries have been performed in 12 cases with Waardenburg syndrome type II in our department from 2000 to 2008. All the patients received multi-channel cochlear implantation through transmastoid facial recess approach. The postoperative outcomes of 12 cases were compared with 12 cases with no inner ear malformation as a control group. The electrodes were totally inserted into the cochlear successfully, there was no facial paralysis and cerebrospinal fluid leakage occurred after operation. The hearing threshold in this series were similar to that of the normal cochlear implantation. After more than half a year of speech rehabilitation, the abilities of speech discrimination and spoken language of all the patients were improved compared with that of preoperation. Multi-channel cochlear implantation could be performed in the cases with Waardenburg syndrome, preoperative hearing and images assessments should be done.

Prenatal diagnosis and genetic counseling in a case of spina bifida in a family with Waardenburg syndrome type I.

PubMed

Kujat, Annegret; Veith, Veit-Peter; Faber, Renaldo; Froster, Ursula G

2007-01-01

Waardenburg syndrome type I (WS I) is an autosomal dominant inherited disorder with an incidence of 1:45,000 in Europe. Mutations within the PAX3 gene are responsible for the clinical phenotype ranging from mild facial features to severe malformations detectable in prenatal diagnosis. Here, we report a four-generation family with several affected members showing various symptoms of WS I. We diagnosed the syndrome first in a pregnant young woman; she was referred because of a spina bifida in prenatal diagnosis. We performed clinical genetic investigations and molecular genetic analysis in all available family members. The phenotype displays a wide intra-familial clinical variability of pigmentary disturbances, facial anomalies and developmental defects. Molecular studies identified a novel splice site mutation within the PAX3 gene in intron 5 in all affected family members, but in none of the unaffected relatives. This case demonstrates the prenatal diagnosis of spina bifida in a fetus which leads to the initial diagnosis of WS I. Further studies could identify a private splice site mutation within the PAX3 gene responsible for the phenotype in this family.

A 725 kb deletion at 22q13.1 chromosomal region including SOX10 gene in a boy with a neurologic variant of Waardenburg syndrome type 2.

PubMed

Siomou, Elisavet; Manolakos, Emmanouil; Petersen, Michael; Thomaidis, Loretta; Gyftodimou, Yolanda; Orru, Sandro; Papoulidis, Ioannis

2012-11-01

Waardenburg syndrome (WS) is a rare (1/40,000) autosomal dominant disorder resulting from melanocyte defects, with varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four clinical subtypes (WS1-S4). Six genes have been identified to be associated with the different subtypes of WS, among which SOX10, which is localized within the region 22q13.1. Lately it has been suggested that whole SOX10 gene deletions can be encountered when testing for WS. In this study we report a case of a 13-year-old boy with a unique de novo 725 kb deletion within the 22q13.1 chromosomal region, including the SOX10 gene and presenting clinical features of a neurologic variant of WS2. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Waardenburg syndrome with extended aganglionosis: report of 3 new cases.

PubMed

Karaca, Irfan; Turk, Erdal; Ortac, Ragip; Kandirici, Aliye

2009-06-01

The Waardenburg-Shah syndrome is an autosomal recessive disease with varied penetration where Hirschsprung's disease and the Waardenburg syndrome are seen together. Although the length of the involved intestinal segment varies in this syndrome, most patients had total colonic aganglionosis with or without small bowel involvement. We present in this study 2 siblings and one first-degree relative for a total of 3 male patients with Waardenburg syndrome and total colonic aganglionosis with or without small bowel involvement, together with their clinical characteristics and treatment methods. The patients who presented with intestinal obstruction findings within the first 48 hours after birth were operated on with 2 patients under elective conditions and 1 as an emergency. The ganglionic segment lengths were 6, 8, and 20 cm, respectively. Aganglionic enterostomy was performed, and the Ziegler operation was used for these patients. The enterostomies started to function on the third postoperative week, and they started to gain weight. However, all died because of sepsis on the 5th to 12th month. Waardenburg-Shah syndrome patients have a higher incidence of total colonic aganglionosis with or without small bowel involvement. The Ziegler operation may be used in patients with inadequate ganglionic bowel length to gain some time for the child to grow and to decrease total parenteral nutrition complications.

Identification of a Novel De Novo Variant in the PAX3 Gene in Waardenburg Syndrome by Diagnostic Exome Sequencing: The First Molecular Diagnosis in Korea.

PubMed

Jang, Mi-Ae; Lee, Taeheon; Lee, Junnam; Cho, Eun-Hae; Ki, Chang-Seok

2015-05-01

Waardenburg syndrome (WS) is a clinically and genetically heterogeneous hereditary auditory pigmentary disorder characterized by congenital sensorineural hearing loss and iris discoloration. Many genes have been linked to WS, including PAX3, MITF, SNAI2, EDNRB, EDN3, and SOX10, and many additional genes have been associated with disorders with phenotypic overlap with WS. To screen all possible genes associated with WS and congenital deafness simultaneously, we performed diagnostic exome sequencing (DES) in a male patient with clinical features consistent with WS. Using DES, we identified a novel missense variant (c.220C>G; p.Arg74Gly) in exon 2 of the PAX3 gene in the patient. Further analysis by Sanger sequencing of the patient and his parents revealed a de novo occurrence of the variant. Our findings show that DES can be a useful tool for the identification of pathogenic gene variants in WS patients and for differentiation between WS and similar disorders. To the best of our knowledge, this is the first report of genetically confirmed WS in Korea.

Identification of a Novel De Novo Variant in the PAX3 Gene in Waardenburg Syndrome by Diagnostic Exome Sequencing: The First Molecular Diagnosis in Korea

PubMed Central

Jang, Mi-Ae; Lee, Taeheon; Lee, Junnam

2015-01-01

Waardenburg syndrome (WS) is a clinically and genetically heterogeneous hereditary auditory pigmentary disorder characterized by congenital sensorineural hearing loss and iris discoloration. Many genes have been linked to WS, including PAX3, MITF, SNAI2, EDNRB, EDN3, and SOX10, and many additional genes have been associated with disorders with phenotypic overlap with WS. To screen all possible genes associated with WS and congenital deafness simultaneously, we performed diagnostic exome sequencing (DES) in a male patient with clinical features consistent with WS. Using DES, we identified a novel missense variant (c.220C>G; p.Arg74Gly) in exon 2 of the PAX3 gene in the patient. Further analysis by Sanger sequencing of the patient and his parents revealed a de novo occurrence of the variant. Our findings show that DES can be a useful tool for the identification of pathogenic gene variants in WS patients and for differentiation between WS and similar disorders. To the best of our knowledge, this is the first report of genetically confirmed WS in Korea. PMID:25932447

[Waardenburg syndrome--ophthalmic findings and criteria for diagnosis: case reports].

PubMed

Nasser, Luciano Sólia; Paranaíba, Lívia Maris Ribeiro; Frota, Ana Cláudia; Gomes, Andreia; Versiani, Gisele; Martelli Júnior, Hercílio

2012-10-01

To describe the clinical and imaginological features of two families with Waardenburg syndrome: type I and II, with emphasis on ophthalmic manifestations, as well as the pattern of genetic inheritance. We conducted a clinical study involving two families affected by Waardenburg syndrome, and through the pedigree, determined the present pattern of genetic inheritance. Analyses were performed including the measurement of visual acuity, the presence of dystopia cantorum (telecanthus), evaluation of iris color and retinal mapping, as well as dermatological and otological examinations. The pedigree of the family affected by the Waardenburg syndrome type I showed an autosomal dominant mode of transmission. The syndrome was present at 85.71% of patients. The dystopia cantorum was the most frequent feature, followed by the white streak on the skin of the forehead, hypopigmentation of the iris and retina and deafness. The Waardenburg syndrome family type II had 33.33% of family members affected by the syndrome. No member had dystopia cantorum and hypopigmentation of the iris. Three patients had sensorineural hearing loss (12.5%), associated with white forelock and achromatic spots confluent by the body. This study shows the importance of the ophthalmologist in aiding the diagnosis of this rare genetic condition, since it includes ocular disorders such as telecanthus, hypopigmentation of the iris and retina. The cantorum dystopia is the main diagnostic criterion to differentiate type I and II syndrome and should be done by a trained ophthalmologist. The families are in medical monitoring, receiving genetic guidelines and care related to eye protection.

SLUG (SNAI2) deletions in patients with Waardenburg disease.

PubMed

Sánchez-Martín, Manuel; Rodríguez-García, Arancha; Pérez-Losada, Jesús; Sagrera, Ana; Read, Andrew P; Sánchez-García, Isidro

2002-12-01

Waardenburg syndrome (WS; deafness with pigmentary abnormalities) is a congenital disorder caused by defective function of the embryonic neural crest. Depending on additional symptoms, WS is classified into four types: WS1, WS2, WS3 and WS4. WS1 and WS3 are caused by mutations in PAX3, whereas WS2 is heterogenous, being caused by mutations in the microphthalmia (MITF) gene in some but not all affected families. The identification of Slugh, a zinc-finger transcription factor expressed in migratory neural crest cells, as the gene responsible for pigmentary disturbances in mice prompted us to analyse the role of its human homologue SLUG in neural crest defects. Here we show that two unrelated patients with WS2 have homozygous deletions in SLUG which result in absence of the SLUG product. We further show that Mitf is present in Slug-deficient cells and transactivates the SLUG promoter, and that Slugh and Kit genetically interact in vivo. Our findings further define the locus heterogeneity of WS2 and point to an essential role of SLUG in the development of neural crest-derived human cell lineages: its absence causes the auditory-pigmentary symptoms in at least some individuals with WS2.

Trauma due to Self-aggression in Patient with Waardenburg Syndrome associated with Congenital Anomalies.

PubMed

Marta, Sara Nader; Kawakami, Roberto Yoshio; Sgavioli, Claudia Almeida Prado Piccino; Correa, Ana Eliza; D'Árk de Oliveira El Kadre, Guaniara; Carvalho, Ricardo Sandri

2016-08-01

Waardenburg syndrome (WS) is an inherited autosomal dominant genetic disorder presenting variable penetrance and expressivity, with an estimated prevalence of 1:42,000. Clinical characteristics of WS include lateral displacement of the internal eye canthus, hyperplasia of the medial portion of the eyebrows, prominent and broad nasal base, congenital deafness, pigmentation of the iris and skin, and white forelock. A 24-year-old male patient, previously diagnosed with WS, was referred to the Special Needs Dental Clinic of Sacred Heart University, Bauru, Brazil. Parents reported that the patient was experiencing self-mutilation, particularly in the oral region. He presented multiple congenital anomalies, including anophthalmia, mental retardation, low-set ears, and leg deformities. Clinical oral examination revealed hypodontia, abnormalities in dental morphology, extensive dental caries, periodontal disease, and fistulae. Extensive scars on the tongue, lips, and hands caused by self-mutilation were also observed. In accordance with his family and neurologist, full-mouth extraction under general anesthesia was performed, especially considering his severe self-aggressive behavior and the necessity to be fed with soft-food diet due to his inability to chew. After the surgical procedure, a significant reduction in the patient's irritability and gain of weight were reported in the follow-ups of 30, 60, and 180 days.

Novel mutations of PAX3, MITF, and SOX10 genes in Chinese patients with type I or type II Waardenburg syndrome.

PubMed

Chen, Hongsheng; Jiang, Lu; Xie, Zhiguo; Mei, Lingyun; He, Chufeng; Hu, Zhengmao; Xia, Kun; Feng, Yong

2010-06-18

Waardenburg syndrome (WS) is a rare disorder characterized by distinctive facial features, pigment disturbances, and sensorineural deafness. There are four WS subtypes. WS1 is mostly caused by PAX3 mutations, while MITF, SNAI2, and SOX10 mutations are associated with WS2. More than 100 different disease-causing mutations have been reported in many ethnic groups, but the data from Chinese patients with WS remains poor. Herein we report 18 patients from 15 Chinese WS families, in which five cases were diagnosed as WS1 and the remaining as WS2. Clinical evaluation revealed intense phenotypic variability in Chinese WS patients. Heterochromia iridis and sensorineural hearing loss were the most frequent features (100% and 88.9%, respectively) of the two subtypes. Many brown freckles on normal skin could be a special subtype of cutaneous pigment disturbances in Chinese WS patients. PAX3, MITF, SNAI2, and SOX10 genes mutations were screened for in all the patients. A total of nine mutations in 11 families were identified and seven of them were novel. The SOX10 mutations in WS2 were first discovered in the Chinese population, with an estimated frequency similar to that of MITF mutations, implying SOX10 is an important pathogenic gene in Chinese WS2 cases and should be considered for first-step analysis in WS2, as well as MITF. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Nonsense mutations in the PAX3 gene cause Waardenburg syndrome type I in two Chinese patients.

PubMed

Yang, Shu-Zhi; Cao, Ju-Yang; Zhang, Rui-Ning; Liu, Li-Xian; Liu, Xin; Zhang, Xin; Kang, Dong-Yang; Li, Mei; Han, Dong-Yi; Yuan, Hui-Jun; Yang, Wei-Yan

2007-01-05

Waardenburg syndrome type I (WS1) is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmental abnormalities of the eye, hair and skin, and dystopia canthorum. The gene mainly responsible for WS1 is PAX3 which is involved in melanocytic development and survival. Mutations of PAX3 have been reported in familiar or sporadic patients with WS1 in several populations of the world except Chinese. In order to explore the genetic background of Chinese WS1 patients, a mutation screening of PAX3 gene was carried out in four WS1 pedigrees. A questionnaire survey and comprehensive clinical examination were conducted in four Chinese pedigrees of WS1. Genomic DNA from each patient and their family members was extracted and exons of PAX3 were amplified by PCR. PCR fragments were ethanol-purified and sequenced in both directions on an ABI_Prism 3100 DNA sequencer with the BigDye Terminator Cycle Sequencing Ready Reaction Kit. The sequences were obtained and aligned to the wild type sequence of PAX3 with the GeneTool program. Two nonsense PAX3 mutations have been found in the study population. One is heterozygous for a novel nonsense mutation S209X. The other is heterozygous for a previously reported mutation in European population R223X. Both mutations create stop codons leading to truncation of the PAX3 protein. This is the first demonstration of PAX3 mutations in Chinese WS1 patients and one of the few examples of an identical mutation of PAX3 occurred in different populations.

Congenital stapes malformation: Rare conductive hearing loss in a patient with Waardenburg syndrome.

PubMed

Melzer, Jonathan M; Eliason, Michael; Conley, George S

2016-04-01

Waardenburg syndrome is a known autosomal dominant cause of congenital hearing loss. It is characterized by a distinctive phenotypic appearance and often involves sensorineural hearing loss. Temporal bone abnormalities and inner ear dysmorphisms have been described in association with the disease. However, middle ear abnormalities as causes of conductive hearing loss are not typically seen in Waardenburg syndrome. We discuss a case of an 8-year-old female who meets diagnostic criteria for Waardenburg syndrome type 3 and who presented with a bilateral conductive hearing loss associated with congenital stapes fixation. We discuss management strategy in this previously unreported phenotype. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Prenatal diagnosis and genetic counseling for Waardenburg syndrome type I and II in Chinese families

PubMed Central

Wang, Li; Qin, Litao; Li, Tao; Liu, Hongjian; Ma, Lingcao; Li, Wan; Wu, Dong; Wang, Hongdan; Guo, Qiannan; Guo, Liangjie; Liao, Shixiu

2018-01-01

Waardenburg syndrome (WS) is an auditory-pigmentary disorder with varying combinations of sensorineural hearing loss and abnormal pigmentation. The present study aimed to investigate the underlying molecular pathology and provide a method of prenatal diagnosis of WS in Chinese families. A total of 11 patients with WS from five unrelated Chinese families were enrolled. A thorough clinical examination was performed on all participants. Furthermore, patients with WS underwent screening for mutations in the following genes: Paired box 3 (PAX3), melanogenesis associated transcription factor (MITF), SRY-box 10, snail family transcriptional repressor 2 and endothelin receptor type B using polymerase chain reaction sequencing. Array-based comparative genomic hybridization was used for specific patients whose sequence results were normal. Following identification of the genotype of the probands and their parents, prenatal genetic diagnosis was performed for family 01 and 05. According to the diagnostic criteria for WS, five cases were diagnosed as WS1, while the other six cases were WS2. Genetic analysis revealed three mutations, including a nonsense mutation PAX3 c.583C>T in family 01, a splice-site mutation MITF c.909G>A in family 03 and an in-frame deletion MITF c.649_651delGAA in family 05. To the best of the authors' knowledge the mutations (c.583C>T in PAX3 and c.909G>A in MITF) were reported for the first time in Chinese people. Mutations in the gene of interest were not identified in family 02 and 04. The prenatal genetic testing of the two fetuses was carried out and demonstrated that the two babies were normal. The results of the present study expanded the range of known genetic mutations in China. Identification of genetic mutations in these families provided an efficient way to understand the causes of WS and improved genetic counseling. PMID:29115496

[A case report on Waardenburg syndrome with cleft lip].

PubMed

Traoré, H; Traoré, D; Ouane, O; Simpara, B; Ongoiba, N

2011-01-01

The syndrome of Waardenburg is a congenital plurimal formatif unit rare described and individualized for the first time by Waardenburg in 1951. It associates in its form most typical dystopie canthale intern, a widening of the base of the nose, disorders of the pigmentation. We wanted brought back this case because of its scarcity. It was about a 18 month old infant without particular antecedents, which was drawn up to us for correction of congenital malformation. The interrogation did not make it possible to find signs functional notable. With the examination it had a general good state. t presented a bilateral iridal hypochromy, a dystopie canthale, a canitie, a bilateral labial slit. The diagnosis of presumption was the Syndrome of Waardenburg because of the description of at least 2 major signs: dystopie canthale and disorders of the pigmentation. The complementary examinations carried out were those of the preoperative assessment which returned normal. The biological diagnosis which rests on the search for change of gene was not made for reasons of technical order and financier. The surgery is centered on the treatment of the labial slit. A chéiloplastie according to Millard was carried out. The continuations were simple. The Syndrome of Waardenburg is a rare, hereditary entity. A neurosensory deafness, musculo-skeletal anomalies, thus qu' a disease of Hirschsprung will have to be systematically required. The surgery of the slit or the télécanthus allows an social integration of the subjects reached.

A novel mutation of PAX3 in a Chinese family with Waardenburg syndrome.

PubMed

Qin, Wei; Shu, Anli; Qian, Xueqing; Gao, Jianjun; Xing, Qinghe; Zhang, Juan; Zheng, Yonglan; Li, Xingwang; Li, Sheng; Feng, Guoyin; He, Lin

2006-08-28

The molecular characterization of 34 members of a Chinese family, with 22 members in four generations, affected with Waardenburg syndrome (WS1). A detailed family history and clinical data were collected. A genome-wide scan by two-point linkage analysis using more than 400 microsatellite markers in combination with haplotype analysis was performed. Mutation screening was carried out in the candidate gene by sequencing of amplified products. A maximum two-point lod score of 6.53 at theta = 0.00 was obtained with marker D2S2248. Haplotype analysis placed the WS1 locus to a 45.74 cM region between D2S117 and D2S206, in close proximity to the PAX3 gene on chromosome 2q35. Mutation screening in PAX3 identified a 701T > C mutation which converted a highly conserved Leu to Pro. This nucleotide alteration was neither seen in unaffected members of the family nor found in 50 unrelated control subjects. The present study identified a novel 701T > C mutation in PAX3. The mutation observed in this family highlights the phenotypic heterogeneity of the disorder.

Spectrum of novel mutations found in Waardenburg syndrome types 1 and 2: implications for molecular genetic diagnostics

PubMed Central

Wildhardt, Gabriele; Zirn, Birgit; Graul-Neumann, Luitgard M; Wechtenbruch, Juliane; Suckfüll, Markus; Buske, Annegret; Bohring, Axel; Kubisch, Christian; Vogt, Stefanie; Strobl-Wildemann, Gertrud; Greally, Marie; Bartsch, Oliver; Steinberger, Daniela

2013-01-01

Objectives Till date, mutations in the genes PAX3 and MITF have been described in Waardenburg syndrome (WS), which is clinically characterised by congenital hearing loss and pigmentation anomalies. Our study intended to determine the frequency of mutations and deletions in these genes, to assess the clinical phenotype in detail and to identify rational priorities for molecular genetic diagnostics procedures. Design Prospective analysis. Patients 19 Caucasian patients with typical features of WS underwent stepwise investigation of PAX3 and MITF. When point mutations and small insertions/deletions were excluded by direct sequencing, copy number analysis by multiplex ligation-dependent probe amplification was performed to detect larger deletions and duplications. Clinical data and photographs were collected to facilitate genotype–phenotype analyses. Setting All analyses were performed in a large German laboratory specialised in genetic diagnostics. Results 15 novel and 4 previously published heterozygous mutations in PAX3 and MITF were identified. Of these, six were large deletions or duplications that were only detectable by copy number analysis. All patients with PAX3 mutations had typical phenotype of WS with dystopia canthorum (WS1), whereas patients with MITF gene mutations presented without dystopia canthorum (WS2). In addition, one patient with bilateral hearing loss and blue eyes with iris stroma dysplasia had a de novo missense mutation (p.Arg217Ile) in MITF. MITF 3-bp deletions at amino acid position 217 have previously been described in patients with Tietz syndrome (TS), a clinical entity with hearing loss and generalised hypopigmentation. Conclusions On the basis of these findings, we conclude that sequencing and copy number analysis of both PAX3 and MITF have to be recommended in the routine molecular diagnostic setting for patients, WS1 and WS2. Furthermore, our genotype–phenotype analyses indicate that WS2 and TS correspond to a clinical spectrum

Multimodal Ultrawide-Field Imaging Features in Waardenburg Syndrome.

PubMed

Choudhry, Netan; Rao, Rajesh C

2015-06-01

A 45-year-old woman was referred for bilateral irregular fundus pigmentation. Dilated fundus examination revealed irregular hypopigmentation posterior to the equator in both eyes, confirmed by fundus autofluorescence. A thickened choroid was seen on enhanced-depth imaging spectral-domain optical coherence tomography (EDI SD-OCT). Systemic evaluation revealed sensorineural deafness, telecanthus, and a white forelock. Further investigation revealed a first-degree relative with Waardenburg syndrome. Waardenburg syndrome is characterized by a group of features including telecanthus, a broad nasal root, synophrys of the eyebrows, piedbaldism, heterochromia irides, and deafness. Choroidal hypopigmentation is a unique feature that can be visualized with ultrawide-field fundus autofluorescence. The choroid may also be thickened and its thickness measured with EDI SD-OCT. Copyright 2015, SLACK Incorporated.

Anophthalmia-Waardenburg syndrome: a report of three cases.

PubMed

Suyugül, Z; Seven, M; Hacihanefioğlu, S; Kartal, A; Suyugül, N; Cenani, A

1996-04-24

We report on 2 Turkish families with children who had bilateral anophthalmia, upper and lower limb abnormalities, mental retardation and consanguineous parents. We have evaluated the 2 cases in the first family and the only case in the second as anophthalmia-Waardenburg syndrome. This is an extremely rare autosomal recessive syndrome.

A Novel Pathogenic Variant in the MITF Gene Segregating with a Unique Spectrum of Ocular Findings in an Extended Iranian Waardenburg Syndrome Kindred

PubMed Central

Jalilian, Nazanin; Tabatabaiefar, Mohammad A.; Bahrami, Tayyeb; Karbasi, Golaleh; Bahramian, Mohammad H.; Salimpoor, Abdolrahman; Noori-Daloii, Mohammad R.

2017-01-01

Waardenburg syndrome (WS) is a rare genetic disorder characterized by abnormal pigmentation of the hair, skin, and iris as well as sensorineural hearing loss. WS is subdivided into 4 major types (WS1–4), where WS2 is characterized by the absence of dystopia canthorum. This study was launched to investigate clinical and molecular characteristics of WS in an extended Iranian WS2 family. A comprehensive clinical investigation was performed. Peripheral blood samples were collected and genomic DNA was extracted. Affected members of the family were studied for possible mutations within the SOX10, MITF, and SNAI2 genes. Six WS2 individuals affected from a large Iranian WS2 kindred were enrolled. All affected members carried the novel substitution c.877C>T at exon 9 in the MITF gene, which resulted in p.Arg293* at the protein level. None of the healthy members and also of 50 ethnically matched controls had this variant. In addition, a spectrum of unique ocular findings, including nystagmus, chorioretinal degeneration, optic disc hypoplasia, astigmatism, and myopia, was segregated with the mutant allele in the pedigree. Our data provide insight into the genotypic and phenotypic spectrum of WS2 in an Iranian family and could further expand the spectrum of MITF mutations and have implications for genetic counseling on WS in Iran. PMID:28690485

A Novel Pathogenic Variant in the MITF Gene Segregating with a Unique Spectrum of Ocular Findings in an Extended Iranian Waardenburg Syndrome Kindred.

PubMed

Jalilian, Nazanin; Tabatabaiefar, Mohammad A; Bahrami, Tayyeb; Karbasi, Golaleh; Bahramian, Mohammad H; Salimpoor, Abdolrahman; Noori-Daloii, Mohammad R

2017-06-01

Waardenburg syndrome (WS) is a rare genetic disorder characterized by abnormal pigmentation of the hair, skin, and iris as well as sensorineural hearing loss. WS is subdivided into 4 major types (WS1-4), where WS2 is characterized by the absence of dystopia canthorum. This study was launched to investigate clinical and molecular characteristics of WS in an extended Iranian WS2 family. A comprehensive clinical investigation was performed. Peripheral blood samples were collected and genomic DNA was extracted. Affected members of the family were studied for possible mutations within the SOX10 , MITF , and SNAI2 genes. Six WS2 individuals affected from a large Iranian WS2 kindred were enrolled. All affected members carried the novel substitution c.877C>T at exon 9 in the MITF gene, which resulted in p.Arg293* at the protein level. None of the healthy members and also of 50 ethnically matched controls had this variant. In addition, a spectrum of unique ocular findings, including nystagmus, chorioretinal degeneration, optic disc hypoplasia, astigmatism, and myopia, was segregated with the mutant allele in the pedigree. Our data provide insight into the genotypic and phenotypic spectrum of WS2 in an Iranian family and could further expand the spectrum of MITF mutations and have implications for genetic counseling on WS in Iran.

A novel mutation in the MITF may be digenic with GJB2 mutations in a large Chinese family of Waardenburg syndrome type II.

PubMed

Yan, Xukun; Zhang, Tianyu; Wang, Zhengmin; Jiang, Yi; Chen, Yan; Wang, Hongyan; Ma, Duan; Wang, Lei; Li, Huawei

2011-12-20

Waardenburg syndrome type II (WS2) is associated with syndromic deafness. A subset of WS2, WS2A, accounting for approximately 15% of patients, is attributed to mutations in the microphthalmia-associated transcription factor (MITF) gene. We examined the genetic basis of WS2 in a large Chinese family. All 9 exons of the MITF gene, the single coding exon (exon 2) of the most common hereditary deafness gene GJB2 and the mitochondrial DNA (mtDNA) 12S rRNA were sequenced. A novel heterozygous mutation c.[742_743delAAinsT;746_747delCA] in exon 8 of the MITF gene co-segregates with WS2 in the family. The MITF mutation results in a premature termination codon and a truncated MITF protein with only 247 of the 419 wild type amino acids. The deaf proband had this MITF gene heterozygous mutation as well as a c.[109G>A]+[235delC] compound heterozygous pathogenic mutation in the GJB2 gene. No pathogenic mutation was found in mtDNA 12S rRNA in this family. Thus, a novel compound heterozygous mutation, c.[742_743delAAinsT;746_747delCA] in MITF exon 8 was the key genetic reason for WS2 in this family, and a digenic effect of MITF and GJB2 genes may contribute to deafness of the proband. Copyright © 2011. Published by Elsevier Ltd.

EPHA4 haploinsufficiency is responsible for the short stature of a patient with 2q35-q36.2 deletion and Waardenburg syndrome.

PubMed

Li, Chuan; Chen, Rongyu; Fan, Xin; Luo, Jingsi; Qian, Jiale; Wang, Jin; Xie, Bobo; Shen, Yiping; Chen, Shaoke

2015-04-11

Waardenburg syndrome type I (WS1), an auditory-pigmentary genetic disorder, is caused by heterozygous loss-of-function mutations in PAX3. Abnormal physical signs such as dystopia canthorum, patchy hypopigmentation and sensorineural hearing loss are common, but short stature is not associated with WS1. We reported a 4-year and 6 month-old boy with a rare combination of WS1 and severe short stature (83.5 cm (-5.8SD)). His facial features include dystopia canthorum, mild synophrys, slightly up-slanted palpebral fissure, posteriorly rotated ears, alae nasi hypoplasia and micrognathia. No heterochromia was noticed. He had a normal intelligence quotient and hearing. Insulin-like growth factor-1 (IGF-1) was 52.7 ng/ml, lower than the normal range (55 ~ 452 ng/ml) and the peak growth hormone level was 7.57 ng/ml at 90 minutes after taking moderate levodopa and pyridostigmine bromide. The patient exhibited a good response to human growth hormone (rhGH) replacement therapy, showing a 9.2 cm/year growth rate and an improvement of 1 standard deviation (SD) of height after one year treatment. CMA test of patient's DNA revealed a 4.46 Mb de novo deletion at 2q35-q36.2 (hg19; chr2:221,234,146-225,697,363). PAX3 haploinsufficiency is known to cause Waardenburg syndrome. Examining overlapping deletions in patients led to the conclusion that EPHA4 is a novel short stature gene. The finding is supported by the splotch-retarded and epha4 knockout mouse models which both showed growth retardation. We believe this rare condition is caused by the haploinsufficiency of both PAX3 and EPH4 genes. We further reported a growth response to recombinant human growth hormone treatment in this patient.

De novo dominant mutation of SOX10 gene in a Chinese family with Waardenburg syndrome type II.

PubMed

Chen, Kaitian; Zong, Ling; Liu, Min; Zhan, Yuan; Wu, Xuan; Zou, Wenting; Jiang, Hongyan

2014-06-01

Waardenburg syndrome is a rare genetic disorder, inherited as an autosomal dominant trait. The condition is characterized by sensorineural hearing loss and pigment disturbances of the hair, skin, and iris. The de novo mutation in the SOX10 gene, responsible for Waardenburg syndrome type II, is rarely seen. The present study aimed to identify the genetic causes of Waardenburg syndrome type II in a Chinese family. Clinical and molecular evaluations were conducted in a Chinese family with Waardenburg syndrome type II. A novel SOX10 heterozygous c.259-260delCT mutation was identified. Heterozygosity was not observed in the parents and sister of the proband, indicating that the mutation has arisen de novo. The novel frameshift mutation, located in exon 3 of the SOX10 gene, disrupted normal amino acid coding from Leu87, leading to premature termination at nucleotide 396 (TGA). The high mobility group domain of SOX10 was inferred to be partially impaired. The novel heterozygous c.259-260delCT mutation in the SOX10 gene was considered to be the cause of Waardenburg syndrome in the proband. The clinical and genetic characterization of this family would help elucidate the genetic heterogeneity of SOX10 in Waardenburg syndrome type II. Moreover, the de novo pattern expanded the mutation data of SOX10. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Genetic analysis of an Indian family with members affected with Waardenburg syndrome and Duchenne muscular dystrophy

PubMed Central

Kapoor, Saketh; Bindu, Parayil Sankaran; Taly, Arun B.; Sinha, Sanjib; Gayathri, Narayanappa; Rani, S. Vasantha; Chandak, Giriraj Ratan

2012-01-01

Purpose Waardenburg syndrome (WS) is characterized by sensorineural hearing loss and pigmentation defects of the eye, skin, and hair. It is caused by mutations in one of the following genes: PAX3 (paired box 3), MITF (microphthalmia-associated transcription factor), EDNRB (endothelin receptor type B), EDN3 (endothelin 3), SNAI2 (snail homolog 2, Drosophila) and SOX10 (SRY-box containing gene 10). Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the DMD gene. The purpose of this study was to identify the genetic causes of WS and DMD in an Indian family with two patients: one affected with WS and DMD, and another one affected with only WS. Methods Blood samples were collected from individuals for genomic DNA isolation. To determine the linkage of this family to the eight known WS loci, microsatellite markers were selected from the candidate regions and used to genotype the family. Exon-specific intronic primers for EDN3 were used to amplify and sequence DNA samples from affected individuals to detect mutations. A mutation in DMD was identified by multiplex PCR and multiplex ligation-dependent probe amplification method using exon-specific probes. Results Pedigree analysis suggested segregation of WS as an autosomal recessive trait in the family. Haplotype analysis suggested linkage of the family to the WS4B (EDN3) locus. DNA sequencing identified a novel missense mutation p.T98M in EDN3. A deletion mutation was identified in DMD. Conclusions This study reports a novel missense mutation in EDN3 and a deletion mutation in DMD in the same Indian family. The present study will be helpful in genetic diagnosis of this family and increases the mutation spectrum of EDN3. PMID:22876130

Genetic analysis of an Indian family with members affected with Waardenburg syndrome and Duchenne muscular dystrophy.

PubMed

Kapoor, Saketh; Bindu, Parayil Sankaran; Taly, Arun B; Sinha, Sanjib; Gayathri, Narayanappa; Rani, S Vasantha; Chandak, Giriraj Ratan; Kumar, Arun

2012-01-01

Waardenburg syndrome (WS) is characterized by sensorineural hearing loss and pigmentation defects of the eye, skin, and hair. It is caused by mutations in one of the following genes: PAX3 (paired box 3), MITF (microphthalmia-associated transcription factor), EDNRB (endothelin receptor type B), EDN3 (endothelin 3), SNAI2 (snail homolog 2, Drosophila) and SOX10 (SRY-box containing gene 10). Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the DMD gene. The purpose of this study was to identify the genetic causes of WS and DMD in an Indian family with two patients: one affected with WS and DMD, and another one affected with only WS. Blood samples were collected from individuals for genomic DNA isolation. To determine the linkage of this family to the eight known WS loci, microsatellite markers were selected from the candidate regions and used to genotype the family. Exon-specific intronic primers for EDN3 were used to amplify and sequence DNA samples from affected individuals to detect mutations. A mutation in DMD was identified by multiplex PCR and multiplex ligation-dependent probe amplification method using exon-specific probes. Pedigree analysis suggested segregation of WS as an autosomal recessive trait in the family. Haplotype analysis suggested linkage of the family to the WS4B (EDN3) locus. DNA sequencing identified a novel missense mutation p.T98M in EDN3. A deletion mutation was identified in DMD. This study reports a novel missense mutation in EDN3 and a deletion mutation in DMD in the same Indian family. The present study will be helpful in genetic diagnosis of this family and increases the mutation spectrum of EDN3.

Molecular basis of splotch and Waardenburg Pax-3 mutations.

PubMed Central

Chalepakis, G; Goulding, M; Read, A; Strachan, T; Gruss, P

1994-01-01

Pax genes control certain aspects of development, as mutations result in (semi)dominant defects apparent during embryogenesis. Pax-3 has been associated with the mouse mutant splotch (Sp) and the human Waardenburg syndrome type 1 (WS1). We have examined the molecular basis of splotch and WS1 by studying the effect of mutations on DNA binding, using a defined target sequence. Pax-3 contains two different types of functional DNA-binding domains, a paired domain and a homeodomain. Mutational analysis of Pax-3 reveals different modes of DNA binding depending on the presence of these domains. A segment of Pax-3 located between the two DNA-binding domains, including a conserved octapeptide, participates in protein homodimerization. Pax-3 mutations found in splotch alleles and WS1 individuals change DNA binding and, in the case of a protein product of the Sp allele, dimerization. These findings were taken as a basis to define the molecular nature of the mutants. Images PMID:7909605

Prenatal diagnosis and genetic counseling for Waardenburg syndrome type I and II in Chinese families.

PubMed

Wang, Li; Qin, Litao; Li, Tao; Liu, Hongjian; Ma, Lingcao; Li, Wan; Wu, Dong; Wang, Hongdan; Guo, Qiannan; Guo, Liangjie; Liao, Shixiu

2018-01-01

Waardenburg syndrome (WS) is an auditory‑pigmentary disorder with varying combinations of sensorineural hearing loss and abnormal pigmentation. The present study aimed to investigate the underlying molecular pathology and provide a method of prenatal diagnosis of WS in Chinese families. A total of 11 patients with WS from five unrelated Chinese families were enrolled. A thorough clinical examination was performed on all participants. Furthermore, patients with WS underwent screening for mutations in the following genes: Paired box 3 (PAX3), melanogenesis associated transcription factor (MITF), SRY‑box 10, snail family transcriptional repressor 2 and endothelin receptor type B using polymerase chain reaction sequencing. Array‑based comparative genomic hybridization was used for specific patients whose sequence results were normal. Following identification of the genotype of the probands and their parents, prenatal genetic diagnosis was performed for family 01 and 05. According to the diagnostic criteria for WS, five cases were diagnosed as WS1, while the other six cases were WS2. Genetic analysis revealed three mutations, including a nonsense mutation PAX3 c.583C>T in family 01, a splice‑site mutation MITF c.909G>A in family 03 and an in‑frame deletion MITF c.649_651delGAA in family 05. To the best of the authors' knowledge the mutations (c.583C>T in PAX3 and c.909G>A in MITF) were reported for the first time in Chinese people. Mutations in the gene of interest were not identified in family 02 and 04. The prenatal genetic testing of the two fetuses was carried out and demonstrated that the two babies were normal. The results of the present study expanded the range of known genetic mutations in China. Identification of genetic mutations in these families provided an efficient way to understand the causes of WS and improved genetic counseling.

Identification of a novel mutation in the paired domain of PAX3 in an Iranian family with waardenburg syndrome type I.

PubMed

Sotirova, V N; Rezaie, T M; Khoshsorour, M M; Sarfarazi, M

2000-03-01

Waardenburg syndrome Type I (WS1) is an autosomal dominant disorder that has previously been associated with mutations in the PAX3 gene on the 2q35 region. In this study, we used an Iranian WS1 family with seven affected individuals in three generations. The phenotypic characteristics of the family include sensorineural deafness, dystopia canthorum, hypopigmented skin patches of the upper limbs, congenital white forelock, confluent white eyebrows, nonpigmented iris, poliosis, and hypopigmentation of the retina. Herein, we report a previously unidentified single-base substitution in exon II (C-->T at position 218) that results in a change of serine to leucine (S73L) in this family. This change was not observed in 100 chromosomes of healthy unrelated individuals. This mutation is within the PAX3 paired domain region, a structure that is highly conserved and implicated in DNA binding. This is the first identification of a PAX3 mutation for this phenotype in the Iranian population. This also provides additional confirmation for the involvement of this gene in the etiology of WS1.

Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is a phosphorylation site with functional significance.

PubMed

Takeda, K; Takemoto, C; Kobayashi, I; Watanabe, A; Nobukuni, Y; Fisher, D E; Tachibana, M

2000-01-01

MITF (microphthalmia-associated transcription factor) is a basic-helix-loop-helix-leucine zipper (bHLHZip) factor which regulates expression of tyrosinase and other melanocytic genes via a CATGTG promoter sequence, and is involved in melanocyte differentiation. Mutations of MITF in mice or humans with Waardenburg syndrome type 2 (WS2) often severely disrupt the bHLHZip domain, suggesting the importance of this structure. Here, we show that Ser298, which locates downstream of the bHLHZip and was previously found to be mutated in individuals with WS2, plays an important role in MITF function. Glycogen synthase kinase 3 (GSK3) was found to phosphorylate Ser298 in vitro, thereby enhancing the binding of MITF to the tyrosinase promoter. The same serine was found to be phosphorylated in vivo, and expression of dominant-negative GSK3beta selectively suppressed the ability of MITF to transactivate the tyrosinase promoter. Moreover, mutation of Ser298, as found in a WS2 family, disabled phos-phorylation of MITF by GSK3beta and impaired MITF function. These findings suggest that the Ser298 is important for MITF function and is phosphorylated probably by GSK3beta.

Identification and functional analysis of a novel mutation in the SOX10 gene associated with Waardenburg syndrome type IV.

PubMed

Wang, Hong-Han; Chen, Hong-Sheng; Li, Hai-Bo; Zhang, Hua; Mei, Ling-Yun; He, Chu-Feng; Wang, Xing-Wei; Men, Mei-Chao; Jiang, Lu; Liao, Xin-Bin; Wu, Hong; Feng, Yong

2014-03-15

Waardenburg syndrome type IV (WS4) is a rare genetic disorder, characterized by auditory-pigmentary abnormalities and Hirschsprung disease. Mutations of the EDNRB gene, EDN3 gene, or SOX10 gene are responsible for WS4. In the present study, we reported a case of a Chinese patient with clinical features of WS4. In addition, the three genes mentioned above were sequenced in order to identify whether mutations are responsible for the case. We revealed a novel nonsense mutation, c.1063C>T (p.Q355*), in the last coding exon of SOX10. The same mutation was not found in three unaffected family members or 100 unrelated controls. Then, the function and mechanism of the mutation were investigated in vitro. We found both wild-type (WT) and mutant SOX10 p.Q355* were detected at the expected size and their expression levels are equivalent. The mutant protein also localized in the nucleus and retained the DNA-binding activity as WT counterpart; however, it lost its transactivation capability on the MITF promoter and acted as a dominant-negative repressor impairing function of the WT SOX10. Copyright © 2014 Elsevier B.V. All rights reserved.

Identification of a Novel De Novo Heterozygous Deletion in the SOX10 Gene in Waardenburg Syndrome Type II Using Next-Generation Sequencing.

PubMed

Li, Haonan; Jin, Peng; Hao, Qian; Zhu, Wei; Chen, Xia; Wang, Ping

2017-11-01

Waardenburg syndrome (WS) is a rare autosomal dominant disorder associated with pigmentation abnormalities and sensorineural hearing loss. In this study, we investigated the genetic cause of WSII in a patient and evaluated the reliability of the targeted next-generation exome sequencing method for the genetic diagnosis of WS. Clinical evaluations were conducted on the patient and targeted next-generation sequencing (NGS) was used to identify the candidate genes responsible for WSII. Multiplex ligation-dependent probe amplification (MLPA) and real-time quantitative polymerase chain reaction (qPCR) were performed to confirm the targeted NGS results. Targeted NGS detected the entire deletion of the coding sequence (CDS) of the SOX10 gene in the WSII patient. MLPA results indicated that all exons of the SOX10 heterozygous deletion were detected; no aberrant copy number in the PAX3 and microphthalmia-associated transcription factor (MITF) genes was found. Real-time qPCR results identified the mutation as a de novo heterozygous deletion. This is the first report of using a targeted NGS method for WS candidate gene sequencing; its accuracy was verified by using the MLPA and qPCR methods. Our research provides a valuable method for the genetic diagnosis of WS.

A novel homozygous variant in the SMOC1 gene underlying Waardenburg anophthalmia syndrome.

PubMed

Ullah, Asmat; Umair, Muhammad; Ahmad, Farooq; Muhammad, Dost; Basit, Sulman; Ahmad, Wasim

2017-01-01

Waardenburg anophthalmia syndrome (WAS), also known as ophthalmo-acromelic syndrome or anophthalmia-syndactyly, is a rare congenital disorder that segregates in an autosomal recessive pattern. Clinical features of the syndrome include malformation of the eyes and the skeleton. Mostly, WAS is caused by mutations in the SMOC-1 gene. The present report describes a large consanguineous family of Pakistani origin segregating Waardenburg anophthalmia syndrome in an autosomal recessive pattern. Genotyping followed by Sanger sequencing was performed to search for a candidate gene. SNP genotyping using AffymetrixGeneChip Human Mapping 250K Nsp array established a single homozygous region among affected members on chromosome 14q23.1-q24.3 harboring the SMOC1 gene. Sequencing of the gene revealed a novel homozygous missense mutation (c.812G>A; p.Cys271Tyr) in the family. This is the first report of Waardenburg anophthalmia syndrome caused by a SMOC1 variant in a Pakistani population. The mutation identified in the present investigation extends the body of evidence implicating the gene SMOC-1 in causing WAS.

PAX3 mutations and clinical characteristics in Chinese patients with Waardenburg syndrome type 1

PubMed Central

Wang, Juan; Li, Shiqiang; Xiao, Xueshan; Wang, Panfeng; Guo, Xiangming

2010-01-01

Purpose To detect paired box gene 3 (PAX3) mutations and associated phenotypes in Chinese patients with Waardenburg syndrome type 1 (WS1). Methods Five unrelated families with suspected WS1 were selected from our Genomic DNA Repository for Hereditary Eye Diseases. The coding and adjacent intronic regions of PAX3 were amplified by polymerase chain reaction and the amplicons were then analyzed by cycle sequencing. Variations detected were further evaluated in available family members as well as one hundred controls with heteroduplex-single strand conformational polymorphism (heteroduplex-SSCP) analysis and/or clone sequencing. Results Three novel and two known mutations in PAX3 were detected in five patients, respectively: c.567_586+17del (p.Asp189_Gln505delinsGluGlyGlyAlaLeuAlaGly), c.456_459dupTTCC (p.Ile154PhefsX162), c.795_800delCTGGTT (p.Trp266_Phe267del), c.799T>A (p.Phe267Ile), and c.667C>T (p.Arg223X). Two novel mutations proved to be de novo as their parents did not carry the mutations. All five patients with PAX3 mutations had dystopia canthorum and different iris color and fundi between their two eyes. However, none had white forelock, skin hypopigmentation, and deafness. Conclusions Our findings expand the frequency and spectrum of PAX3 mutations and ethnic-related phenotypes in Chinese patients with WS1. De novo mutations in PAX3 have not been reported before. PMID:20664692

PAX3 mutations and clinical characteristics in Chinese patients with Waardenburg syndrome type 1.

PubMed

Wang, Juan; Li, Shiqiang; Xiao, Xueshan; Wang, Panfeng; Guo, Xiangming; Zhang, Qingjiong

2010-06-22

To detect paired box gene 3 (PAX3) mutations and associated phenotypes in Chinese patients with Waardenburg syndrome type 1 (WS1). Five unrelated families with suspected WS1 were selected from our Genomic DNA Repository for Hereditary Eye Diseases. The coding and adjacent intronic regions of PAX3 were amplified by polymerase chain reaction and the amplicons were then analyzed by cycle sequencing. Variations detected were further evaluated in available family members as well as one hundred controls with heteroduplex-single strand conformational polymorphism (heteroduplex-SSCP) analysis and/or clone sequencing. Three novel and two known mutations in PAX3 were detected in five patients, respectively: c.567_586+17del (p.Asp189_Gln505delinsGluGlyGlyAlaLeuAlaGly), c.456_459dupTTCC (p.Ile154PhefsX162), c.795_800delCTGGTT (p.Trp266_Phe267del), c.799T>A (p.Phe267Ile), and c.667C>T (p.Arg223X). Two novel mutations proved to be de novo as their parents did not carry the mutations. All five patients with PAX3 mutations had dystopia canthorum and different iris color and fundi between their two eyes. However, none had white forelock, skin hypopigmentation, and deafness. Our findings expand the frequency and spectrum of PAX3 mutations and ethnic-related phenotypes in Chinese patients with WS1. De novo mutations in PAX3 have not been reported before.

Multi-Modal Ultra-Widefield Imaging Features in Waardenburg Syndrome

PubMed Central

Choudhry, Netan; Rao, Rajesh C.

2015-01-01

Background Waardenburg syndrome is characterized by a group of features including; telecanthus, a broad nasal root, synophrys of the eyebrows, piedbaldism, heterochromia irides, and deaf-mutism. Hypopigmentation of the choroid is a unique feature of this condition examined with multi-modal Ultra-Widefield Imaging in this report. Material/Methods Report of a single case. Results Bilateral symmetric choroidal hypopigmentation was observed with hypoautofluorescence in the region of hypopigmentation. Fluorescein angiography revealed a normal vasculature, however a thickened choroid was seen on Enhanced-Depth Imaging Spectral-Domain OCT (EDI SD-OCT). Conclusion(s) Choroidal hypopigmentation is a unique feature of Waardenburg syndrome, which can be visualized with ultra-widefield fundus autofluorescence. The choroid may also be thickened in this condition and its thickness measured with EDI SD-OCT. PMID:26114849

Waardenburg syndrome: clinical differentiation between types I and II.

PubMed

Pardono, Eliete; van Bever, Yolande; van den Ende, Jenneke; Havrenne, Poti C; Iughetti, Paula; Maestrelli, Sylvia R P; Costa F, Orozimbo; Richieri-Costa, Antonio; Frota-Pessoa, Oswaldo; Otto, Paulo A

2003-03-15

Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with the I variant, 21 having the type II, and 8 of them being isolated cases without telecanthus. These patients belong to 37 families; the main contributions and conclusions are based on the detailed study of 25 of these families, examined using standard procedures. All patients were examined as to the presence of eight cardinal signs important for the diagnosis of the condition; from each patient, from many of his/her normal relatives, and from a control sample of 300 normal individuals stratified by age and sex, 23 different craniofacial measurements were obtained. We also estimated, using our own data as well those collected from the literature, the frequencies of the cardinal signs, based on a total sample of 461 affected individuals with WSI and 121 with WSII. In order to originate discriminant functions to separate individuals affected by one of the two variants, both metric (from craniofacial measurements) as well as categoric data (based on the frequencies of the cardinal signs or symptoms) were used. Discriminant analysis based on the frequency of the eight cardinal signs can improve the separation of WSI patients without telecanthus from those presenting the variant II. We present also a Table with the conditional probabilities favoring the diagnosis of WSI for suspect subjects without telecanthus and any combination of the other seven signs/symptoms. The discriminant function based on the four ocular measurements (inner and outer intercanthal, interpupillary, and inferior lacrymal distances), on the other side, perfectly classifies patients affected by one of the variants of WS, the same taking place when the average values of the W index of all affected individuals per family are used. The discriminant function based solely in the individual W index values of patients correctly classifies 93% of WSII subjects, but only 60% of the patients with the

Waardenburg syndrome: iris and choroidal hypopigmentation: findings on anterior and posterior segment imaging.

PubMed

Shields, Carol L; Nickerson, Stephanie J; Al-Dahmash, Saad; Shields, Jerry A

2013-09-01

Waardenburg syndrome typically manifests with congenital iris pigmentary abnormalities, but careful inspection can reveal additional posterior uveal pigmentary abnormalities. To demonstrate iris and choroidal hypopigmentation in patients with Waardenburg syndrome. Retrospective review of 7 patients referred for evaluation of presumed ocular melanocytosis. To describe the clinical and imaging features of the anterior and posterior uvea. In all patients, the diagnosis of Waardenburg syndrome was established. The nonocular features included white forelock in 4 of 7 (57%), tubular nose in 5 of 6 (83%), and small nasal alae in 5 of 6 (83%) patients. In 2 patients, a hearing deficit was documented on audiology testing. Family history of Waardenburg syndrome was elicited in 5 of 7 (71%) patients. Ocular features (7 patients) included telecanthus in 5 (71%), synophrys in 2 (29%), iris hypopigmentation in 5 (71%), and choroidal hypopigmentation in 5 (71%) patients. No patient had muscle contractures or Hirschsprung disease. Visual acuity was 20/20 to 20/50 in all patients. Iris hypopigmentation in 8 eyes was sector in 6 (75%) and diffuse (complete) in 2 (25%). Choroidal hypopigmentation in 9 eyes (100%) showed a sector pattern in 6 (67%) and a diffuse pattern in 3 (33%). Anterior segment optical coherence tomography revealed the hypopigmented iris to be thinner and with shallower crypts than the normal iris. Posterior segment optical coherence tomography showed a normal retina in all patients, but the subfoveal choroid in the hypopigmented region was slightly thinner (mean, 197 μm) compared with the opposite normal choroid (243 μm). Fundus autofluorescence demonstrated mild hyperautofluorescence (scleral unmasking) in hypopigmented choroid and no lipofuscin abnormality. Waardenburg syndrome manifests hypopigmentation of the iris and choroid with imaging features showing a slight reduction in the thickness of the affected tissue.

Waardenburg syndrome--a case report.

PubMed

Bansal, Yuvika; Jain, Parul; Goyal, Gaurav; Singh, Malvika; Mishra, Chittranjan

2013-02-01

Waardenburg syndrome is a rare genetic disorder characterized by varying degree of deafness associated with pigmentary anomaly and defects of neural crest cell derived structures. Four subtypes (I-IV) with variable penetrance and gene expression of different clinical features have been described. We report a patient showing constellation of complete heterochromia, dystopia canthorum, white forelock, and synophrys. Other affected family relatives with heterochromia have been depicted in pedigree. Copyright © 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Shah-Waardenburg syndrome: a case highlighting the importance of a holistic approach to assessing a child.

PubMed

Patil, Amogh; Prathyusha, Lanka; Patil, Muganagowda

2017-12-22

We present the case of a 45-day-old child with the chief complaint of failure to pass stools for 10 days. After initial investigation, the patient was found to have Hirschsprung's disease. However, with further examination and analysis, the extremely rare diagnosis of type 4 Waardenburg syndrome was made (also known as Shah-Waardenburg syndrome or Waardenburg-Hirschsprung's disease). © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Correlation between Waardenburg syndrome phenotype and genotype in a population of individuals with identified PAX3 mutations.

PubMed

DeStefano, A L; Cupples, L A; Arnos, K S; Asher, J H; Baldwin, C T; Blanton, S; Carey, M L; da Silva, E O; Friedman, T B; Greenberg, J; Lalwani, A K; Milunsky, A; Nance, W E; Pandya, A; Ramesar, R S; Read, A P; Tassabejhi, M; Wilcox, E R; Farrer, L A

1998-05-01

Waardenburg syndrome (WS) type 1 is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmentary abnormalities of the eye, hair, and skin, and dystopia canthorum. The phenotype is variable and affected individuals may exhibit only one or a combination of several of the associated features. To assess the relationship between phenotype and gene defect, clinical and genotype data on 48 families (271 WS individuals) collected by members of the Waardenburg Consortium were pooled. Forty-two unique mutations in the PAX3 gene, previously identified in these families, were grouped in five mutation categories: amino acid (AA) substitution in the paired domain, AA substitution in the homeodomain, deletion of the Ser-Thr-Pro-rich region, deletion of the homeodomain and the Ser-Thr-Pro-rich region, and deletion of the entire gene. These mutation classes are based on the structure of the PAX3 gene and were chosen to group mutations predicted to have similar defects in the gene product. Association between mutation class and the presence of hearing loss, eye pigment abnormality, skin hypopigmentation, or white forelock was evaluated using generalized estimating equations, which allowed for incorporation of a correlation structure that accounts for potential similarity among members of the same family. Odds for the presence of eye pigment abnormality, white forelock, and skin hypopigmentation were 2, 8, and 5 times greater, respectively, for individuals with deletions of the homeodomain and the Pro-Ser-Thr-rich region compared to individuals with an AA substitution in the homeodomain. Odds ratios that differ significantly from 1.0 for these traits may indicate that the gene products resulting from different classes of mutations act differently in the expression of WS. Although a suggestive association was detected for hearing loss with an odds ratio of 2.6 for AA substitution in the paired domain compared with AA substitution in the homeodomain, this odds

Tetraphocomelia with the Waardenburg syndrome and multiple malformations.

PubMed

Wu, Hue-Tsi; Wainwright, Helen; Beighton, Peter

2009-04-01

A male infant delivered spontaneously at the 29th week of pregnancy had gross tetraphocomelia and features of the Waardenburg syndrome. There were no relevant factors in the pregnancy nor family history. It is possible that microdeletions or contiguous gene defects are involved in the pathogenesis of these malformations.

Chronic constipation recognized as a sign of a SOX10 mutation in a patient with Waardenburg syndrome.

PubMed

Arimoto, Yukiko; Namba, Kazunori; Nakano, Atsuko; Matsunaga, Tatsuo

2014-05-01

Waardenburg syndrome is characterized by hearing loss, pigmentation abnormalities, dysmorphologic features, and neurological phenotypes. Waardenburg syndrome consists of four distinct subtypes, and SOX10 mutations have been identified in type II and type IV. Type IV differs from type II owing to the presence of Hirschsprung disease. We identified a de novo nonsense mutation in SOX10 (p.G39X) in a female pediatric patient with Waardenburg syndrome with heterochromia iridis, profound bilateral sensorineural hearing loss, inner ear malformations, and overall hypopigmentation of the hair without dystopia canthorum. This patient has experienced chronic constipation since she was a neonate, but anorectal manometry showed a normal anorectal reflex. Chronic constipation in this patient was likely to be a consequence of a mild intestinal disorder owing to the SOX10 mutation, and this patient was considered to have a clinical phenotype intermediate between type II and type IV of the syndrome. Chronic constipation may be recognized as indicative of a SOX10 mutation in patients with Waardenburg syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetic counseling for a three-generation Chinese family with Waardenburg syndrome type II associated with a rare SOX10 mutation.

PubMed

Chen, Kaitian; Zong, Ling; Zhan, Yuan; Wu, Xuan; Liu, Min; Jiang, Hongyan

2015-05-01

Waardenburg syndrome is clinically and genetically heterogeneous. The SOX10 mutation related with Waardenburg syndrome type II is rare in Chinese. This study aimed to uncover the genetic causes of Waardenburg syndrome type II in a three-generation family to improve genetic counseling. Complete clinical and molecular evaluations were conducted in a three-generation Han Chinese family with Waardenburg syndrome type II. Targeted genetic counseling was provided to this family. We identified a rare heterozygous dominant mutation c.621C>A (p.Y207X) in SOX10 gene in this family. The premature termination codon occurs in exon 4, 27 residues downstream of the carboxyl end of the high mobility group box. Bioinformatics prediction suggested this variant to be disease-causing, probably due to nonsense-mediated mRNA decay. Useful genetic counseling was given to the family for prenatal guidance. Identification of a rare dominant heterozygous SOX10 mutation c.621C>A in this family provided an efficient way to understand the causes of Waardenburg syndrome type II and improved genetic counseling. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Asymmetric severity of diabetic retinopathy in Waardenburg syndrome.

PubMed

Kashima, Tomoyuki; Akiyama, Hideo; Kishi, Shoji

2011-01-01

A 30-year-old female patient was referred to our institution due to vitreous hemorrhage. Best corrected visual acuity of her right and left eyes at her initial visit was 10/20 and 20/20, respectively. Although hypochromic iris was observed in the superior iris between the 10 and 2 o'clock positions in her right eye, her entire left eye exhibited hypochromic iris. Hypopigmentation of the fundus was seen in the superior part of her right eye. This eye also had a huge neovascularization on the optic disc that was 7 discs in diameter. Conversely, her left fundi showed hypopigmentation of the fundus in the entire region of the left eye, and dot hemorrhages were observed all over the left fundi, although no neovascularization could be seen microscopically. Fluorescein angiography showed a huge neovascularization in the right eye and a tiny neovascularization in the left eye. Gene analysis revealed the presence of the PAX3 gene homeobox domain mutation, which led to her being diagnosed as Waardenburg syndrome type 1. Magnetic resonance angiography showed there was no obstructive region at either of the internal carotid arteries and ophthalmic arteries. The severity of the diabetic retinopathy appeared to be correlated with the degree of hypopigmentation in the posterior fundus. We speculate that hypopigmentation of the fundus in Waardenburg syndrome may be responsible for the reduction in retinal metabolism, which led to a reduction in oxygen consumption and prevented further aggravation of the diabetic retinopathy. Only laser treatments using short wavelengths was effective in this case. While the extinction coefficient for hemoglobin when using green light is higher than when using yellow light, the differences between these wavelengths tend to disappear when oxygenated hemoglobin is present. To the best of the authors' knowledge, this is the first case report of a patient with Waardenburg syndrome and diabetic retinopathy.

[Mutation analysis of seven patients with Waardenburg syndrome].

PubMed

Hao, Ziqi; Zhou, Yongan; Li, Pengli; Zhang, Quanbin; Li, Jiao; Wang, Pengfei; Li, Xiangshao; Feng, Yong

2016-06-01

To perform genetic analysis for 7 patients with Waardenburg syndrome. Potential mutation of MITF, PAX3, SOX10 and SNAI2 genes was screened by polymerase chain reaction and direct sequencing. Functions of non-synonymous polymorphisms were predicted with PolyPhen2 software. Seven mutations, including c.649-651delAGA (p.R217del), c.72delG (p.G24fs), c.185T>C (p.M62T), c.118C>T (p.Q40X), c.422T>C (p.L141P), c.640C>T (p.R214X) and c.28G>T(p.G43V), were detected in the patients. Among these, four mutations of the PAX3 gene (c.72delG, c.185T>C, c.118C>T and c.128G>T) and one SOX10 gene mutation (c.422T>C) were not reported previously. Three non-synonymous SNPs (c.185T>C, c.128G>T and c.422T>C) were predicted as harmful. Genetic mutations have been detected in all patients with Waardenburg syndrome.

Spectrum of temporal bone abnormalities in patients with Waardenburg syndrome and SOX10 mutations.

PubMed

Elmaleh-Bergès, M; Baumann, C; Noël-Pétroff, N; Sekkal, A; Couloigner, V; Devriendt, K; Wilson, M; Marlin, S; Sebag, G; Pingault, V

2013-01-01

Waardenburg syndrome, characterized by deafness and pigmentation abnormalities, is clinically and genetically heterogeneous, consisting of 4 distinct subtypes and involving several genes. SOX10 mutations have been found both in types 2 and 4 Waardenburg syndrome and neurologic variants. The purpose of this study was to evaluate both the full spectrum and relative frequencies of inner ear malformations in these patients. Fifteen patients with Waardenburg syndrome and different SOX10 mutations were studied retrospectively. Imaging was performed between February 2000 and March 2010 for cochlear implant work-up, diagnosis of hearing loss, and/or evaluation of neurologic impairment. Eleven patients had both CT and MR imaging examinations, 3 had MR imaging only, and 1 had CT only. Temporal bone abnormalities were bilateral. The most frequent pattern associated agenesis or hypoplasia of ≥1 semicircular canal, an enlarged vestibule, and a cochlea with a reduced size and occasionally an abnormal shape, but with normal partition in the 13/15 cases that could be analyzed. Three patients lacked a cochlear nerve, bilaterally in 2 patients. In addition, associated abnormalities were found when adequate MR imaging sequences were available: agenesis of the olfactory bulbs (7/8), hypoplastic or absent lacrimal glands (11/14), hypoplastic parotid glands (12/14), and white matter signal anomalies (7/13). In the appropriate clinical context, bilateral agenesis or hypoplasia of the semicircular canals or both, associated with an enlarged vestibule and a cochlear deformity, strongly suggests a diagnosis of Waardenburg syndrome linked to a SOX10 mutation.

Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature.

PubMed

Verheij, Johanna B G M; Sival, Deborah A; van der Hoeven, Johannes H; Vos, Yvonne J; Meiners, Linda C; Brouwer, Oebele F; van Essen, Anthonie J

2006-01-01

Shah-Waardenburg syndrome is a rare congenital disorder with variable clinical expression, characterised by aganglionosis of the rectosigmoïd (Hirschsprung disease), and abnormal melanocyte migration, resulting in pigmentary abnormalities and sensorineural deafness (Waardenburg syndrome). Mutations in the EDN, EDNRB and SOX10 genes can be found in patients with this syndrome. SOX10 mutations are specifically associated with a more severe phenotype called PCWH: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease. Neuronal expression of SOX10 occurs in neural crest cells during early embryonic development and in glial cells of the peripheral and central nervous systems during late embryonic development and in adults. We present a 4-year-old girl with the PCWH phenotype associated with a de novo nonsense mutation (S384X) in SOX10. Main clinical features were mental retardation, peripheral neuropathy, deafness, Hirschsprung disease, distal arthrogryposis, white hairlock, and growth retardation. She presented with hypotonia, developmental delay, reduced peripheral nerve conduction velocities, and radiologically assessed central hypomyelination. Subsequently, the formation of abnormal myelin within the central and peripheral nervous system was functionally and radiologically assessed. Children presenting with features of Waardenburg syndrome and neurological dysfunction should be tested for mutations in the SOX10 gene to enable diagnosis and counselling.

Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2

PubMed Central

Zazo Seco, Celia; Serrão de Castro, Luciana; van Nierop, Josephine W.; Morín, Matías; Jhangiani, Shalini; Verver, Eva J.J.; Schraders, Margit; Maiwald, Nadine; Wesdorp, Mieke; Venselaar, Hanka; Spruijt, Liesbeth; Oostrik, Jaap; Schoots, Jeroen; van Reeuwijk, Jeroen; Lelieveld, Stefan H.; Huygen, Patrick L.M.; Insenser, María; Admiraal, Ronald J.C.; Pennings, Ronald J.E.; Hoefsloot, Lies H.; Arias-Vásquez, Alejandro; de Ligt, Joep; Yntema, Helger G.; Jansen, Joop H.; Muzny, Donna M.; Huls, Gerwin; van Rossum, Michelle M.; Lupski, James R.; Moreno-Pelayo, Miguel Angel; Kunst, Henricus P.M.; Kremer, Hannie

2015-01-01

Linkage analysis combined with whole-exome sequencing in a large family with congenital and stable non-syndromic unilateral and asymmetric hearing loss (NS-UHL/AHL) revealed a heterozygous truncating mutation, c.286_303delinsT (p.Ser96Ter), in KITLG. This mutation co-segregated with NS-UHL/AHL as a dominant trait with reduced penetrance. By screening a panel of probands with NS-UHL/AHL, we found an additional mutation, c.200_202del (p.His67_Cys68delinsArg). In vitro studies revealed that the p.His67_Cys68delinsArg transmembrane isoform of KITLG is not detectable at the cell membrane, supporting pathogenicity. KITLG encodes a ligand for the KIT receptor. Also, KITLG-KIT signaling and MITF are suggested to mutually interact in melanocyte development. Because mutations in MITF are causative of Waardenburg syndrome type 2 (WS2), we screened KITLG in suspected WS2-affected probands. A heterozygous missense mutation, c.310C>G (p.Leu104Val), that segregated with WS2 was identified in a small family. In vitro studies revealed that the p.Leu104Val transmembrane isoform of KITLG is located at the cell membrane, as is wild-type KITLG. However, in culture media of transfected cells, the p.Leu104Val soluble isoform of KITLG was reduced, and no soluble p.His67_Cys68delinsArg and p.Ser96Ter KITLG could be detected. These data suggest that mutations in KITLG associated with NS-UHL/AHL have a loss-of-function effect. We speculate that the mechanism of the mutation underlying WS2 and leading to membrane incorporation and reduced secretion of KITLG occurs via a dominant-negative or gain-of-function effect. Our study unveils different phenotypes associated with KITLG, previously associated with pigmentation abnormalities, and will thereby improve the genetic counseling given to individuals with KITLG variants. PMID:26522471

Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2.

PubMed

Zazo Seco, Celia; Serrão de Castro, Luciana; van Nierop, Josephine W; Morín, Matías; Jhangiani, Shalini; Verver, Eva J J; Schraders, Margit; Maiwald, Nadine; Wesdorp, Mieke; Venselaar, Hanka; Spruijt, Liesbeth; Oostrik, Jaap; Schoots, Jeroen; van Reeuwijk, Jeroen; Lelieveld, Stefan H; Huygen, Patrick L M; Insenser, María; Admiraal, Ronald J C; Pennings, Ronald J E; Hoefsloot, Lies H; Arias-Vásquez, Alejandro; de Ligt, Joep; Yntema, Helger G; Jansen, Joop H; Muzny, Donna M; Huls, Gerwin; van Rossum, Michelle M; Lupski, James R; Moreno-Pelayo, Miguel Angel; Kunst, Henricus P M; Kremer, Hannie

2015-11-05

Linkage analysis combined with whole-exome sequencing in a large family with congenital and stable non-syndromic unilateral and asymmetric hearing loss (NS-UHL/AHL) revealed a heterozygous truncating mutation, c.286_303delinsT (p.Ser96Ter), in KITLG. This mutation co-segregated with NS-UHL/AHL as a dominant trait with reduced penetrance. By screening a panel of probands with NS-UHL/AHL, we found an additional mutation, c.200_202del (p.His67_Cys68delinsArg). In vitro studies revealed that the p.His67_Cys68delinsArg transmembrane isoform of KITLG is not detectable at the cell membrane, supporting pathogenicity. KITLG encodes a ligand for the KIT receptor. Also, KITLG-KIT signaling and MITF are suggested to mutually interact in melanocyte development. Because mutations in MITF are causative of Waardenburg syndrome type 2 (WS2), we screened KITLG in suspected WS2-affected probands. A heterozygous missense mutation, c.310C>G (p.Leu104Val), that segregated with WS2 was identified in a small family. In vitro studies revealed that the p.Leu104Val transmembrane isoform of KITLG is located at the cell membrane, as is wild-type KITLG. However, in culture media of transfected cells, the p.Leu104Val soluble isoform of KITLG was reduced, and no soluble p.His67_Cys68delinsArg and p.Ser96Ter KITLG could be detected. These data suggest that mutations in KITLG associated with NS-UHL/AHL have a loss-of-function effect. We speculate that the mechanism of the mutation underlying WS2 and leading to membrane incorporation and reduced secretion of KITLG occurs via a dominant-negative or gain-of-function effect. Our study unveils different phenotypes associated with KITLG, previously associated with pigmentation abnormalities, and will thereby improve the genetic counseling given to individuals with KITLG variants. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

[Molecular pathogenesis of Waardenburg syndrome type II resulting from SOX10 gene mutation].

PubMed

Zhang, Hua; Chen, Hongsheng; Feng, Yong; Qian, Minfei; Li, Jiping; Liu, Jun; Zhang, Chun

2016-08-01

To explore the molecular mechanism of Waardenburg syndrome type II (WS2) resulting from SOX10 gene mutation E248fs through in vitro experiment. 293T cells were transiently transfected with wild type (WT) SOX10 and mutant type (MT) E248fs plasmids. The regulatory effect of WT/MT SOX10 on the transcriptional activity of MITF gene and influence of E248fs on WT SOX10 function were determined with a luciferase activity assay. The DNA binding capacity of the WT/MT SOX10 with the promoter of the MITF gene was determined with a biotinylated double-stranded oligonucleotide probe containing the SOX10 binding sequence cattgtc to precipitate MITF and E248fs, respectively. The stability of SOX10 and E248fs were also analyzed. As a loss-of-function mutation, the E248fs mutant failed to transactivate the MITF promoter as compared with the WT SOX10 (P<0.01), which also showed a dominant-negative effect on WT SOX10. The WT SOX10 and E248fs mutant were also able to bind specifically to the cattgtc motif in the MITF promoter, whereas E248fs had degraded faster than WT SOX10. Despite the fact that the E248fs has a dominant-negative effect on SOX10, its reduced stability may down-regulate the transcription of MITF and decrease the synthesis of melanin, which may result in haploinsufficiency of SOX10 protein and cause the milder WS2 phenotype.

Waardenburg syndrome type II in a Chinese patient caused by a novel nonsense mutation in the SOX10 gene.

PubMed

Ma, Jing; Zhang, Tie-Song; Lin, Ken; Sun, Hao; Jiang, Hong-Chao; Yang, Yan-Li; Low, Fan; Gao, Ying-Qin; Ruan, Biao

2016-06-01

Waardenburg syndrome is a congenital genetic disorder. It is the most common type of syndromic hearing impairment with highly genetic heterogeneity and proved to be related by 6 genes as follows: PAX3, MITF, SNAI2, EDN3, EDNRB and SOX10. This article aims to identify the genetic causes of a Chinese WS child patient. A Chinese WS child was collected for clinical data collection by questionnaire survey. DNA samples of proband and his parents were extracted from peripheral blood samples. Six candidate genes were sequenced by the Trusight One sequencing panel on the illumina NextSeq 500 platform. A novel nonsense heterozygous mutation was found in the coding region of exon 2 in the SOX10 gene of proband. The novel nonsense heterozygous mutation could cause the replacement of the 55th lysine codon by stop codon (484T > C, C142R) and further more possibly cause terminating the protein translation in advance. However, both proband's parents had no mutation of genes above mentioned. The gene mutation of SOX10 [NM_006941.3 c.163A > T] is a novel nonsense mutation. No record of this mutation has been found in dbSNP, HGMD, 1000 Genomes Project, ClinVar and ESP6500 databases. It meets the condition of PS2 of strong evidence in 2015 ACMG Standards and Guidelines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Phenotypic variability in Waardenburg syndrome resulting from a 22q12.3-q13.1 microdeletion involving SOX10.

PubMed

Jelena, Brezo; Christina, Lam; Eric, Vilain; Fabiola, Quintero-Rivera

2014-06-01

Waardenburg syndrome (WS) is a neurocristopathy characterized by pigmentation abnormalities of the skin, hair, and iris, as well as sensorineural hearing loss. Contiguous gene deletions encompassing SOX10 are rare, which limits conclusions about genotype-phenotype correlation regarding patient prognosis and management. This study adds to the existing body of knowledge by characterizing a 2.4 Mb deletion [arr[hg19] 22q12.3-q13.1 (36467502-38878207)x1] encompassing SOX10 and 53 additional RefSeq genes in a 15-year-old female with atypical WS. The patient presented with developmental delay, profound bilateral sensorineural hearing loss, heterochromia iridis, hypotonia, and bilateral finger contractures. Published genomic and phenotypic profiles of patients with SOX10-encompassing deletions point toward several plausible candidate gene that could account for the considerable clinical heterogeneity. These studies suggest the existence of modifiers among the co-deleted, dosage-sensitive genes (e.g., MYH9) and among genes whose effect may depend on the unmasking of recessive mutations (e.g., PLA2G6). Finally, we highlight evidence illustrating extensive interconnectivity of SOX10-hypothesizing that haploinsufficiency of SOX10 may "unmask" subtler effects on expression or epistasis associated with variants in SOX10 targets (e.g., DHH), in its partners (e.g., PAX3, EGR2), and in genes with functional overlap (e.g., SOX8, SOX9). © 2014 Wiley Periodicals, Inc.

Clinical and genetic investigation of families with type II Waardenburg syndrome

PubMed Central

CHEN, YONG; YANG, FUWEI; ZHENG, HEXIN; ZHOU, JIANDA; ZHU, GANGHUA; HU, PENG; WU, WEIJING

2016-01-01

The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia-associated transcription factor (MITF), sex-determining region Y-box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease-causing mutation in pedigree 1. However, there are novel disease-causing genes in Waardenburg syndrome type II, which require further research. PMID:26781036

Clinical and genetic investigation of families with type II Waardenburg syndrome.

PubMed

Chen, Yong; Yang, Fuwei; Zheng, Hexin; Zhou, Jianda; Zhu, Ganghua; Hu, Peng; Wu, Weijing

2016-03-01

The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia‑associated transcription factor (MITF), sex‑determining region Y‑box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease‑causing mutation in pedigree 1. However, there are novel disease‑causing genes in Waardenburg syndrome type II, which require further research.

A de novo SOX10 mutation causing severe type 4 Waardenburg syndrome without Hirschsprung disease.

PubMed

Sznajer, Yves; Coldéa, Cristina; Meire, Françoise; Delpierre, Isabelle; Sekhara, Tayeb; Touraine, Renaud L

2008-04-15

Type 4 Waardenburg syndrome represents a well define entity caused by neural crest derivatives anomalies (melanocytes, intrinsic ganglion cells, central, autonomous and peripheral nervous systems) leading, with variable expressivity, to pigmentary anomalies, deafness, mental retardation, peripheral neuropathy, and Hirschsprung disease. Autosomal dominant mode of inheritance is prevalent when Sox10 gene mutation is identified. We report the natural history of a child who presented with synophrys, vivid blue eye, deafness, bilateral complete semicircular canals agenesis with mental retardation, subtle signs for peripheral neuropathy and lack of Hirschsprung disease. SOX10 gene sequencing identified "de novo" splice site mutation (c.698-2A > C). The present phenotype and the genotype findings underline the wide spectrum of SOX10 gene implication in unusual type 4 Waardenburg syndrome patient. Copyright 2008 Wiley-Liss, Inc.

Tietz/Waardenburg type 2A syndrome associated with posterior microphthalmos in two unrelated patients with novel MITF gene mutations.

PubMed

Cortés-González, Vianney; Zenteno, Juan Carlos; Guzmán-Sánchez, Martín; Giordano-Herrera, Verónica; Guadarrama-Vallejo, Dalia; Ruíz-Quintero, Narlly; Villanueva-Mendoza, Cristina

2016-12-01

Tietz syndrome and Waardenburg syndrome type 2A are allelic conditions caused by MITF mutations. Tietz syndrome is inherited in an autosomal dominant pattern and is characterized by congenital deafness and generalized skin, hair, and eye hypopigmentation, while Waardenburg syndrome type 2A typically includes variable degrees of sensorineural hearing loss and patches of de-pigmented skin, hair, and irides. In this paper, we report two unrelated families with MITF mutations. The first family showed an autosomal dominant pattern and variable expressivity. The second patient was isolated. MITF gene analysis in the first family demonstrated a c.648A>C heterozygous mutation in exon 8 c.648A>C; p. (R216S), while in the isolated patient, an apparently de novo heterozygous c.1183_1184insG truncating mutation was demonstrated in exon 10. All patients except one had bilateral reduced ocular anteroposterior axial length and a high hyperopic refractive error corresponding to posterior microphthalmos, features that have not been described as part of the disease. Our results suggest that posterior microphthalmos might be part of the clinical characteristics of Tietz/Waardenburg syndrome type 2A and expand both the clinical and molecular spectrum of the disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Molecular Etiology of Hereditary Single-Side Deafness: Its Association With Pigmentary Disorders and Waardenburg Syndrome.

PubMed

Kim, Shin Hye; Kim, Ah Reum; Choi, Hyun Seok; Kim, Min Young; Chun, Eun Hi; Oh, Seung-Ha; Choi, Byung Yoon

2015-10-01

Unilateral sensorineural hearing loss (USNHL)/single-side deafness (SSD) is a frequently encountered disability in children. The etiology of a substantial portion of USNHL/SSD still remains unknown, and genetic causes have not been clearly elucidated. In this study, the authors evaluated the heritability of USNHL/SSD.The authors sequentially recruited 50 unrelated children with SSD. For an etiologic diagnosis, we performed a rigorous review on the phenotypes of family members of all children and conducted, if necessary, molecular genetic tests including targeted exome sequencing of 129 deafness genes.Among the 50 SSD children cohort, the authors identify 4 (8%) unrelated SSD probands from 4 families (SH136, SB173, SB177, and SB199) with another hearing impaired family members. Notably, all 4 probands in our cohort with a familial history of SSD also have pigmentary abnormalities such as brown freckles or premature gray hair within first degree relatives, which may indicate that genes whose products are involved with pigmentary disorder could be candidates for heritable SSD. Indeed, SH136 and SB199 turned out to segregate a mutation in MITF and PAX3, respectively, leading to a molecular diagnosis of Waardenburg syndrome (WS).We report, for the first time in the literature, a significant heritability of pediatric SSD. There is a strong association between the heritability of USNHL/SSD and the pigmentary abnormality, shedding a new light on the understanding of the molecular basis of heritable USNHL/SSD. In case of children with congenital SSD, it would be mandatory to rigorously screen pigmentary abnormalities. WS should also be included in the differential diagnosis of children with USNHL/SSD, especially in a familial form.

A family with unusual Waardenburg syndrome type I (WSI), cleft lip (palate), and Hirschsprung disease is not linked to PAX 3.

PubMed

Pierpont, J W; St Jacques, D; Seaver, L H; Erickson, R P

1995-03-01

An unusual family with Waardenburg syndrome type 1 (WSI), cleft lip (palate), and Hirschsprung disease is not linked to the PAX 3 gene since there is an obligate crossover which has occurred between PAX 3 DNA markers and the disorder in this family. This family may also have anticipation of the WSI traits as the proband's grandmother is nonpenetrant, his mother has dystopia canthorum, and severe cleft lip (palate), while the proband has dystopia canthorum, severe cleft lip (palate), and Hirschsprung disease. Thus, a locus other than PAX 3 is implicated in this Waardenburg-like syndrome with Hirschsprung disease and cleft lip (palate).

[Study of gene mutation and pathogenetic mechanism for a family with Waardenburg syndrome].

PubMed

Chen, Hongsheng; Liao, Xinbin; Liu, Yalan; He, Chufeng; Zhang, Hua; Jiang, Lu; Feng, Yong; Mei, Lingyun

2017-08-10

To explore the pathogenetic mechanism of a family affected with Waardenburg syndrome. Clinical data of the family was collected. Potential mutation of the MITF, SOX10 and SNAI2 genes were screened. Plasmids for wild type (WT) and mutant MITF proteins were constructed to determine their exogenous expression and subcellular distribution by Western blotting and immunofluorescence assay, respectively. A heterozygous c.763C>T (p.R255X) mutation was detected in exon 8 of the MITF gene in the proband and all other patients from the family. No pathological mutation of the SOX10 and SNAI2 genes was detected. The DNA sequences of plasmids of MITF wild and mutant MITF R255X were confirmed. Both proteins were detected with the expected size. WT MITF protein only localized in the nucleus, whereas R255X protein showed aberrant localization in the nucleus as well as the cytoplasm. The c.763C>T mutation of the MITF gene probably underlies the disease in this family. The mutation can affect the subcellular distribution of MITF proteins in vitro, which may shed light on the molecular mechanism of Waardenburg syndrome caused by mutations of the MITF gene.

[Mutation screening of MITF gene in patients with Waardenburg syndrome type 2].

PubMed

Chen, Jing; Yang, Shu-Zhi; Liu, Jun; Han, Bing; Wang, Guo-Jian; Zhang, Xin; Kang, Dong-Yang; Dai, Pu; Young, Wie-Yen; Yuan, Hui-Jun

2008-04-01

Warrgenburg syndrome type 2 (WS2) is the most common autosomal dominantly-inherited syndrome with hearing loss. MITF (microphthalmia associated transcription factor)is a basic-helix-loop-helix-luecine zipper (bHLHZip) factor which regulates expression of tyrosinase, and is involved in melanocyte differentiation. Mutations in MITF associated with WS2 have been identified in some but not all affected families. Here, we report a three-generation Chinese family with a point mutation in the MITF gene causing WS2. The proband exhibits congenital severe sensorineural hearing loss, heterochromia iridis and facial freckles. One of family members manifests sensorineural deafness, and the other patients show premature greying or/and freckles. This mutation, heterozygous deletion c.639delA, creates a stop codon in exon 7 and is predicted to result in a truncated protein lacking normal interaction with its target DNA motif. This mutation is a novel mutation and the third case identified in exon 7 of MITF in WS2. Though there is only one base pair distance between this novel mutation and the other two documented cases and similar amino acids change, significant difference is seen in clinical phenotype, which suggests genetic background may play an important role.

Novel mutation of Endothelin-B receptor gene in Waardenburg-Hirschsprung disease.

PubMed

Sangkhathat, Surasak; Chiengkriwate, Piyawan; Kusafuka, Takeshi; Patrapinyokul, Sakda; Fukuzawa, Masahiro

2005-12-01

Homozygous mutations of EDNRB in human have been reported to result in Waardenburg-Hirschsprung disease (WS4), while mutated heterozygotes manifested isolated Hirschsprung disease in lower penetrance. We investigated a case of WS4 together with all members of her nuclear family for the alteration of the EDNRB gene by using PCR-SSCP and direct sequencing technique. The index patient, who was born to a family with no history of Hirschsprung disease, presented total colonic aganglionosis with small bowel extension, sensorineural hearing loss and generalized cutaneous pigmentary defects. Interestingly, both irides were normally black. The study detected a homozygous missense mutation at codon 196 in exon 2 (Ser196Asn), which has not been reported. Both parents and four in six siblings harbored heterozygous mutation without any clinical manifestation. Our findings were consistent with previous observations that full spectrum of WS4 occurred to the mutate homozygotes. Moreover, the non-penetrance of heterozygotes in our pedigree, which differs from other reports, demonstrates the high pleiotropic effect of EDNRB mutations in human.

Mutations in the SPARC-related modular calcium-binding protein 1 gene, SMOC1, cause waardenburg anophthalmia syndrome.

PubMed

Abouzeid, Hana; Boisset, Gaëlle; Favez, Tatiana; Youssef, Mohamed; Marzouk, Iman; Shakankiry, Nihal; Bayoumi, Nader; Descombes, Patrick; Agosti, Céline; Munier, Francis L; Schorderet, Daniel F

2011-01-07

Waardenburg anophthalmia syndrome, also known as microphthalmia with limb anomalies, ophthalmoacromelic syndrome, and anophthalmia-syndactyly, is a rare autosomal-recessive developmental disorder that has been mapped to 10p11.23. Here we show that this disease is heterogeneous by reporting on a consanguineous family, not linked to the 10p11.23 locus, whose two affected children have a homozygous mutation in SMOC1. Knockdown experiments of the zebrafish smoc1 revealed that smoc1 is important in eye development and that it is expressed in many organs, including brain and somites.

Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation.

PubMed

Chan, Kwok Keung; Wong, Corinne Kung Yen; Lui, Vincent Chi Hang; Tam, Paul Kwong Hang; Sham, Mai Har

2003-10-15

SOX10 is a member of the SOX gene family related by homology to the high-mobility group (HMG) box region of the testis-determining gene SRY. Mutations of the transcription factor gene SOX10 lead to Waardenburg-Hirschsprung syndrome (Waardenburg-Shah syndrome, WS4) in humans. A number of SOX10 mutations have been identified in WS4 patients who suffer from different extents of intestinal aganglionosis, pigmentation, and hearing abnormalities. Some patients also exhibit signs of myelination deficiency in the central and peripheral nervous systems. Although the molecular bases for the wide range of symptoms displayed by the patients are still not clearly understood, a few target genes for SOX10 have been identified. We have analyzed the impact of six different SOX10 mutations on the activation of SOX10 target genes by yeast one-hybrid and mammalian cell transfection assays. To investigate the transactivation activities of the mutant proteins, three different SOX target binding sites were introduced into luciferase reporter gene constructs and examined in our series of transfection assays: consensus HMG domain protein binding sites; SOX10 binding sites identified in the RET promoter; and Sox10 binding sites identified in the P0 promoter. We found that the same mutation could have different transactivation activities when tested with different target binding sites and in different cell lines. The differential transactivation activities of the SOX10 mutants appeared to correlate with the intestinal and/or neurological symptoms presented in the patients. Among the six mutant SOX10 proteins tested, much reduced transactivation activities were observed when tested on the SOX10 binding sites from the RET promoter. Of the two similar mutations X467K and 1400del12, only the 1400del12 mutant protein exhibited an increase of transactivation through the P0 promoter. While the lack of normal SOX10 mediated activation of RET transcription may lead to intestinal aganglionosis

Partial Oculocutaneous Albinism: Two Siblings with Features of both Hermansky Pudlak and Waardenburg's Syndrome.

PubMed

Ishaq, Mazhar; Niazi, Muhammad Khizar; Khan, Muhammad Saim; Nadeem, Yasser

2015-04-01

Albinism is an inherited abnormality of melanin synthesis with incidence of one per 20,000 births. Its clinical manifestations are related to the reduction or absence of pigmentation in the visual system and/or the skin and teguments. The clinical spectrum of Oculocutaneous Albinism (OCA) has four types ranging from OCA 1 - 4, of which OCA 1, A-1 is the most severe form. Partial cutaneous albinism which is a subtype of OCA is associated with systemic immunodeficiency disorders like Chediak Higashi (CHS), Griscelli (GS) and Hermansky-Pudlak (HPS) syndromes. A7 years boy was labeled initially as a case of Hermansky Pudlak syndrome at the age of 01 year. He as well as his 4 years old younger brother when examined in detail along with audiological investigations were diagnosed as a rare presentation of both Hermansky Pudlak and Waardenburg's syndrome.

Novel and recurrent non-truncating mutations of the MITF basic domain: genotypic and phenotypic variations in Waardenburg and Tietz syndromes

PubMed Central

Léger, Sandy; Balguerie, Xavier; Goldenberg, Alice; Drouin-Garraud, Valérie; Cabot, Annick; Amstutz-Montadert, Isabelle; Young, Paul; Joly, Pascal; Bodereau, Virginie; Holder-Espinasse, Muriel; Jamieson, Robyn V; Krause, Amanda; Chen, Hongsheng; Baumann, Clarisse; Nunes, Luis; Dollfus, Hélène; Goossens, Michel; Pingault, Véronique

2012-01-01

The microphthalmia-associated transcription factor (MITF) is a basic helix-loop-helix leucine zipper transcription factor, which regulates melanocyte development and the biosynthetic melanin pathway. A notable relationship has been described between non-truncating mutations of its basic domain and Tietz syndrome, which is characterized by albinoid-like hypopigmentation of the skin and hair, rather than the patchy depigmentation seen in Waardenburg syndrome, and severe hearing loss. Twelve patients with new or recurrent non-truncating mutations of the MITF basic domain from six families were enrolled in this study. We observed a wide range of phenotypes and some unexpected features. All the patients had blue irides and pigmentation abnormalities that ranged from diffuse hypopigmentation to Waardenburg-like patches. In addition, they showed congenital complete hearing loss, diffuse hypopigmentation of the skin, freckling and ocular abnormalities, more frequently than patients with MITF mutations outside the basic domain. In conclusion, the non-truncating mutations of the basic domain do not always lead to Tietz syndrome but rather to a large range of phenotypes. Sun-exposed freckles are interestingly observed more frequently in Asian populations. This variability argues for the possible interaction with modifier loci. PMID:22258527

Waardenburg-Shah Syndrome: a rare case in an Indian child.

PubMed

Pattebahadur, Rajesh; Singhi, Shipra; Maharana, Prafulla Kumar

2016-09-30

A 7-year-old male child presented with a history of discolouration of right eye since birth. On examination visual acuity was 6/6 on Snellen's chart in both eyes; anterior segment was within normal limits except for the brilliant blue discolouration of the inferior quadrant and superior quadrant of right iris and left eye iris, respectively. Both eyes had a clear lens and fundus findings were within normal limits. A detailed history from parents revealed that the child had difficulty in hearing and slurring of speech. In addition, the child had repeated episodes of constipation with bilious vomiting during infancy for which a diagnosis of fungal sepsis with Hirschsprung's disease was made and the child had to undergo a mid-sigmoid loop colostomy for that. A diagnosis of Waardenburg--Shah Syndrome was made and the child was referred for hearing and speech rehabilitation. 2016 BMJ Publishing Group Ltd.

Upregulation of the Nr2f1-A830082K12Rik gene pair in murine neural crest cells results in a complex phenotype reminiscent of Waardenburg syndrome type 4

PubMed Central

Bergeron, Karl-F.; Nguyen, Chloé M. A.; Cardinal, Tatiana; Charrier, Baptiste; Silversides, David W.

2016-01-01

ABSTRACT Waardenburg syndrome is a neurocristopathy characterized by a combination of skin and hair depigmentation, and inner ear defects. In the type 4 form, these defects show comorbidity with Hirschsprung disease, a disorder marked by an absence of neural ganglia in the distal colon, triggering functional intestinal obstruction. Here, we report that the Spot mouse line – obtained through an insertional mutagenesis screen for genes involved in neural crest cell (NCC) development – is a model for Waardenburg syndrome type 4. We found that the Spot insertional mutation causes overexpression of an overlapping gene pair composed of the transcription-factor-encoding Nr2f1 and the antisense long non-coding RNA A830082K12Rik in NCCs through a mechanism involving relief of repression of these genes. Consistent with the previously described role of Nr2f1 in promoting gliogenesis in the central nervous system, we further found that NCC-derived progenitors of the enteric nervous system fail to fully colonize Spot embryonic guts owing to their premature differentiation in glial cells. Taken together, our data thus identify silencer elements of the Nr2f1-A830082K12Rik gene pair as new candidate loci for Waardenburg syndrome type 4. PMID:27585883

Upregulation of the Nr2f1-A830082K12Rik gene pair in murine neural crest cells results in a complex phenotype reminiscent of Waardenburg syndrome type 4.

PubMed

Bergeron, Karl-F; Nguyen, Chloé M A; Cardinal, Tatiana; Charrier, Baptiste; Silversides, David W; Pilon, Nicolas

2016-11-01

Waardenburg syndrome is a neurocristopathy characterized by a combination of skin and hair depigmentation, and inner ear defects. In the type 4 form, these defects show comorbidity with Hirschsprung disease, a disorder marked by an absence of neural ganglia in the distal colon, triggering functional intestinal obstruction. Here, we report that the Spot mouse line - obtained through an insertional mutagenesis screen for genes involved in neural crest cell (NCC) development - is a model for Waardenburg syndrome type 4. We found that the Spot insertional mutation causes overexpression of an overlapping gene pair composed of the transcription-factor-encoding Nr2f1 and the antisense long non-coding RNA A830082K12Rik in NCCs through a mechanism involving relief of repression of these genes. Consistent with the previously described role of Nr2f1 in promoting gliogenesis in the central nervous system, we further found that NCC-derived progenitors of the enteric nervous system fail to fully colonize Spot embryonic guts owing to their premature differentiation in glial cells. Taken together, our data thus identify silencer elements of the Nr2f1-A830082K12Rik gene pair as new candidate loci for Waardenburg syndrome type 4. © 2016. Published by The Company of Biologists Ltd.

A spontaneous and novel Pax3 mutant mouse that models Waardenburg syndrome and neural tube defects.

PubMed

Ohnishi, Tetsuo; Miura, Ikuo; Ohba, Hisako; Shimamoto, Chie; Iwayama, Yoshimi; Wakana, Shigeharu; Yoshikawa, Takeo

2017-04-05

Genes responsible for reduced pigmentation phenotypes in rodents are associated with human developmental defects, such as Waardenburg syndrome, where patients display congenital deafness along with various abnormalities mostly related to neural crest development deficiency. In this study, we identified a spontaneous mutant mouse line Rwa, which displays variable white spots on mouse bellies and white digits and tail, on a C57BL/6N genetic background. Curly tail and spina bifida were also observed, although at a lower penetrance. These phenotypes were dominantly inherited by offspring. We searched for the genetic mechanism of the observed phenotypes. We harnessed a rapid mouse gene mapping system newly developed in our laboratories to identify a responsible gene. We detected a region within chromosome 1 as a probable locus for the causal mutation. Dense mapping using interval markers narrowed the locus down to a 670-kbp region, containing four genes including Pax3, a gene known to be implicated in the types I and III Waardenburg syndrome. Extensive mutation screening of Pax3 detected an 841-bp deletion, spanning the promoter region and intron 1 of the gene. The defective allele of Pax3, named Pax3 Rwa , lacked the first coding exon and co-segregated perfectly with the phenotypes, confirming its causal nature. The genetic background of Rwa mice is almost identical to that of inbred C57BL/6N. These results highlight Pax3 Rwa mice as a beneficial tool for analyzing biological processes involving Pax3, in particular the development and migration of neural crest cells and melanocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

De novo SOX10 Nonsense Mutation in a Patient with Kallmann Syndrome, Deafness, Iris Hypopigmentation, and Hyperthyroidism.

PubMed

Wang, Fang; Zhao, Shaoli; Xie, Yanhong; Yang, Wenjun; Mo, Zhaohui

2018-03-01

Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder characterized by hypogonadotropic hypogonadism and olfactory dysfunction. Recently, mutations in SOX10, a well-known causative gene of Waardenburg syndrome (WS), have been identified in a few KS patients with additional developmental defects including hearing loss. However, the understanding of SOX10 mutation associates with KS and other clinical consequences remains fragmentary. A 30-year-old Chinese male patient presented with no pubertal sex development when he was at the age of twelve years. Additionally, he showed anosmia, sensory deafness, and blue irises. Last year, he developed clinical symptoms of hyperthyroidism with a fast heartbeat, heat intolerance and weight loss. Blood examinations revealed low levels of FSH, LH, and testosterone. Thyroid function showed high levels of FT3, FT4 and extremely low level of TSH. Molecular analysis detected a de novo (c.565G>T/p.E189X) mutation in SOX10, which has previously been reported in a patient with WS4 (WS with Hirschsprung). The mutation was predicted to be probably damaging. These results highlight the significance of SOX10 haploinsufficiency as a genetic cause of KS. Importantly, our result implies that the same SOX10 mutation can underlie both typical KS and WS, while the correlation between SOX10 and hyperthyroidism still needs to be clarified in the future. © 2018 by the Association of Clinical Scientists, Inc.

[Phenotypic and genetic analysis of a patient presented with Tietz/Waardenburg type II a syndrome].

PubMed

Wang, Huanhuan; Tang, Lifang; Zhang, Jingmin; Hu, Qin; Chen, Yingwei; Xiao, Bing

2015-08-01

To determine the genetic cause for a patient featuring decreased pigmentation of the skin and iris, hearing loss and multiple congenital anomalies. Routine chromosomal banding was performed to analyze the karyotype of the patient and his parents. Single nucleotide polymorphism array (SNP array) was employed to identify cryptic chromosome aberrations, and quantitative real-time PCR was used to confirm the results. Karyotype analysis has revealed no obvious anomaly for the patient and his parents. SNP array analysis of the patient has demonstrated a 3.9 Mb deletion encompassing 3p13p14.1, which caused loss of entire MITF gene. The deletion was confirmed by quantitative real-time PCR. Clinical features of the patient have included severe bilateral hearing loss, decreased pigmentation of the skin and iris and multiple congenital anomalies. The patient, carrying a 3p13p14.1 deletion, has features of Tietz syndrome/Waardenburg syndrome type IIa. This case may provide additional data for the study of genotype-phenotype correlation of this disease.

ABCD syndrome is caused by a homozygous mutation in the EDNRB gene.

PubMed

Verheij, Joke B G M; Kunze, Jürgen; Osinga, Jan; van Essen, Anthonie J; Hofstra, Robert M W

2002-03-15

ABCD syndrome is an autosomal recessive syndrome characterized by albinism, black lock, cell migration disorder of the neurocytes of the gut (Hirschsprung disease [HSCR]), and deafness. This phenotype clearly overlaps with the features of the Shah-Waardenburg syndrome, comprising sensorineural deafness; hypopigmentation of skin, hair, and irides; and HSCR. Therefore, we screened DNA of the index patient of the ABCD syndrome family for mutations in the endothelin B receptor (EDNRB) gene, a gene known to be involved in Shah-Waardenburg syndrome. A homozygous nonsense mutation in exon 3 (R201X) of the EDNRB gene was found. We therefore suggest that ABCD syndrome is not a separate entity, but an expression of Shah-Waardenburg syndrome.

22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.

PubMed

Falah, Nadia; Posey, Jennifer E; Thorson, Willa; Benke, Paul; Tekin, Mustafa; Tarshish, Brocha; Lupski, James R; Harel, Tamar

2017-04-01

Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH. © 2017 Wiley Periodicals, Inc.

22q11.2q13 Duplication Including SOX10 causes Sex-reversal and Peripheral Demyelinating Neuropathy, Central Dysmyelinating Leukodystrophy, Waardenburg Syndrome and Hirschsprung Disease

PubMed Central

Falah, Nadia; Posey, Jennifer E.; Thorson, Willa; Benke, Paul; Tekin, Mustafa; Tarshish, Brocha; Lupski, James R; Harel, Tamar

2017-01-01

Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., 2004; Ajmga 127: 149–151], of an individual with 22q duplication and sex-reversal syndrome. The subject’s phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain-of-function rather than dominant negative activity underlies PCWH. PMID:28328136

Sensorineural Deafness, Distinctive Facial Features and Abnormal Cranial Bones

PubMed Central

Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R.; Matsushita, Mark; Raskind, Wendy H.

2008-01-01

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. PMID:18553554

[Waardenburg's syndrome].

PubMed

Gimñenez, F; Carbonell, R; Pérez, F; Lozano, I

1994-01-01

Reporting one case of this condition type-2 with heterochromia iridis and cochlear deafness. The AA. review the syndrome's components and it nomenclature as well. They discuss about the convenience of including this deviation in the chapter of "diseases of the embryonic neural crest". The specific place of the gene responsibly in the chromosome-2 and the possibilities of genetic counselling are considered.

Syndrome in question*

PubMed Central

Peruzzo, Juliano; Nazar, Fernanda Luca; Tubone, Mariana Quirino; Escobar, Gabriela Fortes; Cestari, Tania Ferreira

2015-01-01

Waardenburg syndrome is an inherited disease characterized by sensorineural hearing loss, pigmentation changes and minor facial malformations. It has four clinical variants. We report the case of a girl who, like her mother, was affected by this syndrome. The diagnosis was made after detection and treatment of deafness. PMID:26375234

Coral Pathogens Identified for White Syndrome (WS) Epizootics in the Indo-Pacific

PubMed Central

Sussman, Meir; Willis, Bette L.; Victor, Steven; Bourne, David G.

2008-01-01

Background White Syndrome (WS), a general term for scleractinian coral diseases with acute signs of advancing tissue lesions often resulting in total colony mortality, has been reported from numerous locations throughout the Indo-Pacific, constituting a growing threat to coral reef ecosystems. Methodology/Principal Findings Bacterial isolates were obtained from corals displaying disease signs at three WS outbreak sites: Nikko Bay in the Republic of Palau, Nelly Bay in the central Great Barrier Reef (GBR) and Majuro Atoll in the Republic of the Marshall Islands, and used in laboratory-based infection trials to satisfy Henle-Koch's postulates, Evan's rules and Hill's criteria for establishing causality. Infected colonies produced similar signs to those observed in the field following exposure to bacterial concentrations of 1×106 cells ml−1. Phylogenetic 16S rRNA gene analysis demonstrated that all six pathogens identified in this study were members of the γ-Proteobacteria family Vibrionacae, each with greater than 98% sequence identity with the previously characterized coral bleaching pathogen Vibrio coralliilyticus. Screening for proteolytic activity of more than 150 coral derived bacterial isolates by a biochemical assay and specific primers for a Vibrio family zinc-metalloprotease demonstrated a significant association between the presence of isolates capable of proteolytic activity and observed disease signs. Conclusion/Significance This is the first study to provide evidence for the involvement of a unique taxonomic group of bacterial pathogens in the aetiology of Indo-Pacific coral diseases affecting multiple coral species at multiple locations. Results from this study strongly suggest the need for further investigation of bacterial proteolytic enzymes as possible virulence factors involved in Vibrio associated acute coral infections. PMID:18560584

From genes to brain development to phenotypic behavior: "dorsal-stream vulnerability" in relation to spatial cognition, attention, and planning of actions in Williams syndrome (WS) and other developmental disorders.

PubMed

Atkinson, Janette; Braddick, Oliver

2011-01-01

Visual information is believed to be processed through two distinct, yet interacting cortical streams. The ventral stream performs the computations needed for recognition of objects and faces ("what" and "who"?) and the dorsal stream the computations for registering spatial relationships and for controlling visually guided actions ("where" and "how"?). We initially proposed a model of spatial deficits in Williams syndrome (WS) in which visual abilities subserved by the ventral stream, such as face recognition, are relatively well developed (although not necessarily in exactly the same way as in typical development), whereas dorsal-stream functions, such as visuospatial actions, are markedly impaired. Since these initial findings in WS, deficits of motion coherence sensitivity, a dorsal-stream function has been found in other genetic disorders such as Fragile X and autism, and as a consequence of perinatal events (in hemiplegia, perinatal brain anomalies following very premature birth), leading to the proposal of a general "dorsal-stream vulnerability" in many different conditions of abnormal human development. In addition, dorsal-stream systems provide information used in tasks of visuospatial memory and locomotor planning, and these systems are closely coupled to networks for attentional control. We and several other research groups have previously shown deficits of frontal and parietal lobe function in WS individuals for specific attention tasks [e.g., Atkinson, J., Braddick, O., Anker, S., Curran, W., & Andrew, R. (2003). Neurobiological models of visuospatial cognition in children with Williams Syndrome: Measures of dorsal-stream and frontal function. Developmental Neuropsychology, 23(1/2), 141-174.]. We have used the Test of Everyday Attention for Children (TEA-Ch) which aims to attempt to separate components of attention with distinct brain networks (selective attention, sustained attention, and attention control-executive function) testing a group of older

Cross Syndrome Comparison of Sleep Problems in Children with Down Syndrome and Williams Syndrome

ERIC Educational Resources Information Center

Ashworth, Anna; Hill, Catherine M.; Karmiloff-Smith, Annette; Dimitriou, Dagmara

2013-01-01

Based on previous findings of frequent sleep problems in children with Down syndrome (DS) and Williams syndrome (WS), the present study aimed to expand our knowledge by using parent report and actigraphy to define sleep problems more precisely in these groups. Twenty-two school-aged children with DS, 24 with WS and 52 typically developing (TD)…

A novel mutation in SMOC1 and variable phenotypic expression in two patients with Waardenburg anophthalmia syndrome.

PubMed

Jamshidi, Javad; Abdollahi, Shokoufeh; Ghaedi, Hamid; Alehabib, Elham; Tafakhori, Abbas; Alinaghi, Somayeh; Chapi, Marjan; Johari, Amir Hossein; Darvish, Hossein

2017-11-01

Waardenburg anophthalmia syndrome (WAS) is a rare disorder that mostly affects the eyes and distal limbs. In the current study we reported two Iranian patients with WAS. The first case was a 26-year-old girl with unilateral anophthalmia, bilateral camptodactyly and clinodactyly in her hands, oligodactly in her left foot and syndactyly of the second to fifth toes in her right foot. She also had severe hearing loss in both ears. The second case was a 12-year-old boy with bilateral anophthalmia, camptodactyly in his right hand, oligodactyly in his foot, clubfoot, and cryptorchidism. Both patients were mentally normal. To detect the causative mutation all exons and exon-intron boundaries of SMOC1 gene were sequenced in patients and other normal family members. We found a homozygous missense mutation (NM_001034852.2(SMOC1):c.367T > C) in exon 3 of SMOC1 gene in both patients. As the mutation segregated with the disease in the family, it should be the causative mutation. Our study extended the mutation spectrum of SMOC1 gene related to WAS. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Self Concept in People with Williams Syndrome and Prader-Willi Syndrome

ERIC Educational Resources Information Center

Plesa-Skwerer, Daniela; Sullivan, Kate; Joffre, Kristen; Tager-Flusberg, Helen

2004-01-01

This study explored self concepts in matched groups of adolescents and adults with Williams syndrome (WS) and Prader-Willi syndrome (PWS), using Damon and Hart's [Self-understanding in Childhood and Adolescence, Cambridge University Press, New York, 1988] semi-structured interview. The main findings were that the WS participants were more…

Assessment of oxytetracycline baths as therapeutic treatment for the control of the agent of withering syndrome (WS) in red abalone (Haliotis rufescens).

PubMed

Winkler, Federico M; García, Ricardo; Valdivia, María Vicenta; Lohrmann, Karin B

2018-03-01

Withering Syndrome (WS) is a lethal disease that affects abalone species in both wild and farmed populations. This infection, caused by the rickettsial-like intracellular organism (RLO) Candidatus Xenohaliotis californiensis, can severely impair the normal development of affected animals, and ultimately, their survival. The most common line of action against the WS has been the use of antibiotics, specifically oxytetracycline (OTC), administered via intramuscular injection and per os via medicated feed. In the present study, we have assessed the effectiveness of OTC baths as therapeutic treatment for the control of the WS agent in H. rufescens. Clinical signs of infection were monitored for 11 months in treated juveniles, in addition to feed consumption rate, growth patterns and gonad development. Abalones were asymptomatic until the end of the experiment, when a small number of non-treated animals exhibited clinical signs of infection. Gonad maturity was not observed. OTC treated animals grew significantly less than their non-treated counterparts, being 4.3% shorter and 13.6% lighter at the end of the experiment. They also displayed negative allometry, i.e. for the same shell length, they were lighter than non-treated groups. Furthermore, the weight of muscle and soft tissues in OTC treated animals was lighter than in the other groups, while no differences were found in shell weight. The feed consumption rate was the same for all groups, thus the observed growth patterns cannot be attributed to a decreased feed intake. One possible explanation is that antibiotic treatment may have impacted gut microflora, thus preventing efficient nutrient digestion and absorption and, indirectly, reducing growth. Prevalence of RLOs causing WS (WS-RLO) and the variant form (RLOv), infected with a bacteriophague and non virulent, were significantly lower in the OTC-treated group than in the other groups. Similar results were observed for the mean intensity of RLOv, while for WS

Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice

PubMed Central

Rainger, Joe; van Beusekom, Ellen; Ramsay, Jacqueline K.; McKie, Lisa; Al-Gazali, Lihadh; Pallotta, Rosanna; Saponari, Anita; Branney, Peter; Fisher, Malcolm; Morrison, Harris; Bicknell, Louise; Gautier, Philippe; Perry, Paul; Sokhi, Kishan; Sexton, David; Bardakjian, Tanya M.; Schneider, Adele S.; Elcioglu, Nursel; Ozkinay, Ferda; Koenig, Rainer; Mégarbané, Andre; Semerci, C. Nur; Khan, Ayesha; Zafar, Saemah; Hennekam, Raoul; Sousa, Sérgio B.; Ramos, Lina; Garavelli, Livia; Furga, Andrea Superti; Wischmeijer, Anita; Jackson, Ian J.; Gillessen-Kaesbach, Gabriele; Brunner, Han G.; Wieczorek, Dagmar; van Bokhoven, Hans; FitzPatrick, David R.

2011-01-01

Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1tm1a) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1tm1a/tm1a). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1tm1a/tm1a embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice. PMID:21750680

Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg Anophthalmia) syndrome in humans and mice.

PubMed

Rainger, Joe; van Beusekom, Ellen; Ramsay, Jacqueline K; McKie, Lisa; Al-Gazali, Lihadh; Pallotta, Rosanna; Saponari, Anita; Branney, Peter; Fisher, Malcolm; Morrison, Harris; Bicknell, Louise; Gautier, Philippe; Perry, Paul; Sokhi, Kishan; Sexton, David; Bardakjian, Tanya M; Schneider, Adele S; Elcioglu, Nursel; Ozkinay, Ferda; Koenig, Rainer; Mégarbané, Andre; Semerci, C Nur; Khan, Ayesha; Zafar, Saemah; Hennekam, Raoul; Sousa, Sérgio B; Ramos, Lina; Garavelli, Livia; Furga, Andrea Superti; Wischmeijer, Anita; Jackson, Ian J; Gillessen-Kaesbach, Gabriele; Brunner, Han G; Wieczorek, Dagmar; van Bokhoven, Hans; Fitzpatrick, David R

2011-07-01

Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1(tm1a)) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1(tm1a/tm1a)). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1(tm1a/tm1a) embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice.

The Waardenburg Syndrome Type 4 Gene, SOX10, Is a Novel Tumor-associated Antigen Identified in a Patient with a Dramatic Response to Immunotherapy

PubMed Central

Khong, Hung T.; Rosenberg, Steven A.

2008-01-01

In this study, we have identified, for the first time, the presence of de novo cellular immune reactivity against the transcription factor SOX10, using tumor-infiltrating lymphocytes obtained from a patient who experienced a dramatic clinical response to immunotherapy. SOX10 acts as a critical transactivator of tyrosinase-related protein-2 during melanoblast development and a potent transactivator of micropthalmia-associated transcription factor, which is considered to be a master gene that controls the development and postnatal survival of melanocytes. Mutations in SOX10 result in Waardenburg syndrome type 4. The overlapping epitopes AWISKPPGV and SAWISKPPGV, designated SOX10: 332–340 and SOX10: 331–340, respectively, were recognized by tumor-infiltrating lymphocyte clone M37 in an HLA-A2-restricted fashion. PMID:12036907

A patient with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and severe hypoganglionosis associated with a novel SOX10 mutation.

PubMed

Akutsu, Yuko; Shirai, Kentaro; Takei, Akira; Goto, Yudai; Aoyama, Tomohiro; Watanabe, Akimitu; Imamura, Masatoshi; Enokizono, Takashi; Ohto, Tatsuyuki; Hori, Tetsuo; Suzuki, Keiko; Hayashi, Masaharu; Masumoto, Kouji; Inoue, Ken

2018-05-01

In this report, we present the case of a female infant with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH) associated with a novel frameshift mutation (c.842dupT) in exon 5, the last exon of SOX10. She had severe hypoganglionosis in the small intestine and entire colon, and suffered from frequent enterocolitis. The persistence of ganglion cells made both the diagnosis and treatment difficult in the neonatal period. She also showed hypopigmentation of the irises, hair and skin, bilateral sensorineural deafness with hypoplastic inner year, severe demyelinating neuropathy with hypotonia, and diffuse brain hypomyelination. The p.Ser282GlnfsTer12 mutation presumably escapes from nonsense-mediated decay and may generate a dominant-negative effect. We suggest that hypoganglionosis can be a variant intestinal manifestation associated with PCWH and that hypoganglionosis and aganglionosis may share the same pathoetiological mechanism mediated by SOX10 mutations. © 2018 Wiley Periodicals, Inc.

7 CFR 1781.8 - Rates and terms-WS loans and WS advances and RCD loans.

Code of Federal Regulations, 2010 CFR

2010-01-01

... principal benefits from the WS works of improvement or RCD measure being financed first become available. (3) The useful life of the WS works of improvement or RCD measure being financed with loan or advance... repaid within the life of the reservoir structure but in no event later than 50 years for WS and 30 years...

Congenital heart defects in Williams syndrome.

PubMed

Yuan, Shi-Min

2017-01-01

Yuan SM. Congenital heart defects in Williams syndrome. Turk J Pediatr 2017; 59: 225-232. Williams syndrome (WS), also known as Williams-Beuren syndrome, is a rare genetic disorder involving multiple systems including the circulatory system. However, the etiologies of the associated congenital heart defects in WS patients have not been sufficiently elucidated and represent therapeutic challenges. The typical congenital heart defects in WS were supravalvar aortic stenosis, pulmonary stenosis (both valvular and peripheral), aortic coarctation and mitral valvar prolapse. The atypical cardiovascular anomalies include tetralogy of Fallot, atrial septal defects, aortic and mitral valvular insufficiencies, bicuspid aortic valves, ventricular septal defects, total anomalous pulmonary venous return, double chambered right ventricle, Ebstein anomaly and arterial anomalies. Deletion of the elastin gene on chromosome 7q11.23 leads to deficiency or abnormal deposition of elastin during cardiovascular development, thereby leading to widespread cardiovascular abnormalities in WS. In this article, the distribution, treatment and surgical outcomes of typical and atypical cardiac defects in WS are discussed.

Novel route to WOx nanorods and WS2 nanotubes from WS2 inorganic fullerenes.

PubMed

Li, Yan-Hui; Zhao, Yi Min; Ma, Ren Zhi; Zhu, Yan Qiu; Fisher, Niles; Jin, Yi Zheng; Zhang, Xin Ping

2006-09-21

WO(x) (2 < x < 3) and WS(2) nanostructures have been widely praised due to applications as catalysts, solid lubricants, field emitters, and optical components. Many methods have been developed to fabricate these nanomaterials; however, most attention was focused on the same dimensional transformation from WO(x) nanoparticles or nanorods to WS(2) nanoparticles or nanotubes. In a solid-vapor reaction, by simply controlling the quantity of water vapor and reaction temperature, we have realized the transformation from quasi-zero-dimensional WS(2) nanoparticles to one-dimensional W(18)O(49) nanorods, and subsequent sulfuration reactions have further converted these W(18)O(49) nanorods into WS(2) nanotubes. The reaction temperature, quantity of water vapor, and pretreatment of the WS(2) nanoparticle precursors are important process parameters for long, thin, and homogeneous W(18)O(49) nanorods growth. The morphologies, crystal structures, and circling transformation mechanisms of sulfide-oxide-sulfide are discussed, and the photoluminescence properties of the resulting nanorods are investigated using a Xe lamp under an excitation of 270 nm.

Fabrication of WS2/GaN p-n Junction by Wafer-Scale WS2 Thin Film Transfer.

PubMed

Yu, Yang; Fong, Patrick W K; Wang, Shifeng; Surya, Charles

2016-11-29

High quality wafer-scale free-standing WS 2 grown by van der Waals rheotaxy (vdWR) using Ni as a texture promoting layer is reported. The microstructure of vdWR grown WS 2 was significantly modified from mixture of crystallites with their c-axes both parallel to (type I) and perpendicular to (type II) the substrate to large type II crystallites. Wafer-scale transfer of vdWR grown WS 2 onto different substrates by an etching-free technique was demonstrated for the first time that utilized the hydrophobic property of WS 2 and hydrophilic property of sapphire. Our results show that vdWR is a reliable technique to obtain type-II textured crystallites in WS 2 , which is the key factor for the wafer-scale etching-free transfer. The transferred films were found to be free of observable wrinkles, cracks, or polymer residues. High quality p-n junctions fabricated by room-temperature transfer of the p-type WS 2 onto an n-type GaN was demonstrated with a small leakage current density of 29.6 μA/cm 2 at -1 V which shows superior performances compared to the directly grown WS 2 /GaN heterojunctions.

Genes and Syndromic Hearing Loss.

ERIC Educational Resources Information Center

Keats, Bronya J. B.

2002-01-01

This article provides a description of the human genome and patterns of inheritance and discusses genes that are associated with some of the syndromes for which hearing loss is a common finding, including: Waardenburg, Stickler, Jervell and Lange-Neilsen, Usher, Alport, mitochondrial encephalomyopathy, and sensorineural hearing loss. (Contains…

Facial emotion recognition in Williams syndrome and Down syndrome: A matching and developmental study.

PubMed

Martínez-Castilla, Pastora; Burt, Michael; Borgatti, Renato; Gagliardi, Chiara

2015-01-01

In this study both the matching and developmental trajectories approaches were used to clarify questions that remain open in the literature on facial emotion recognition in Williams syndrome (WS) and Down syndrome (DS). The matching approach showed that individuals with WS or DS exhibit neither proficiency for the expression of happiness nor specific impairments for negative emotions. Instead, they present the same pattern of emotion recognition as typically developing (TD) individuals. Thus, the better performance on the recognition of positive compared to negative emotions usually reported in WS and DS is not specific of these populations but seems to represent a typical pattern. Prior studies based on the matching approach suggested that the development of facial emotion recognition is delayed in WS and atypical in DS. Nevertheless, and even though performance levels were lower in DS than in WS, the developmental trajectories approach used in this study evidenced that not only individuals with DS but also those with WS present atypical development in facial emotion recognition. Unlike in the TD participants, where developmental changes were observed along with age, in the WS and DS groups, the development of facial emotion recognition was static. Both individuals with WS and those with DS reached an early maximum developmental level due to cognitive constraints.

Behavioural profile and maternal stress in Greek young children with Williams syndrome.

PubMed

Papaeliou, C; Polemikos, N; Fryssira, E; Kodakos, A; Kaila, M; Yiota, X; Benaveli, E; Michaelides, C; Stroggilos, V; Vrettopoulou, M

2012-11-01

Williams syndrome (WS) is a genetic disorder causing intellectual disability. Children with WS often exhibit various kinds of maladaptive behaviours that affect their social functioning. In order to determine whether these behaviours are syndrome-specific, it would be necessary to compare children with WS with children with other syndromes as well as to provide data on the socio-emotional profile in WS from a variety of cultures. The present study investigated the behavioural profile and its relation to maternal stress in Greek young children with WS in comparison with young children with Down syndrome and typically developing (TD) children. Participants were 60 mothers, 20 in each syndrome group and 20 in the control group. The three groups were matched for mental age. The behavioural profile of the participants was investigated through the Child Behaviour Checklist (1.5-5 years) and maternal stress through the Parental Stress Index. In accordance with studies in other cultures, it was found that young children with WS received significantly higher rates in emotional problems and anxiety/depression, compared with both children with Down syndrome and TD children. Moreover, mothers of children with WS reported significantly higher scores in the Total Stress index compared with mothers of TD children. However, in contrast with previous studies, only 25% of children with WS fell into the clinical range in the total Child Behavior Checklist score. The consistency of the socio-emotional characteristics of children with WS across cultures and developmental stages implies a strong influence of the genetic phenotype. However, Greek mothers avoided to characterize these behaviours as pathological. Implications of these findings for clinical practice are also discussed. © 2011 Blackwell Publishing Ltd.

Pathways to Language: A Naturalistic Study of Children with Williams Syndrome and Children with Down Syndrome

ERIC Educational Resources Information Center

Levy, Yonata; Eilam, Ariela

2013-01-01

This is a naturalistic study of the development of language in Hebrew-speaking children with Williams syndrome (WS) and children with Down syndrome (DS), whose MLU extended from 1[multiplied by]0 to 4[multiplied by]4. Developmental curves over the entire span of data collection revealed minor differences between children with WS, children with DS,…

WS2 mode-locked ultrafast fiber laser

PubMed Central

Mao, Dong; Wang, Yadong; Ma, Chaojie; Han, Lei; Jiang, Biqiang; Gan, Xuetao; Hua, Shijia; Zhang, Wending; Mei, Ting; Zhao, Jianlin

2015-01-01

Graphene-like two dimensional materials, such as WS2 and MoS2, are highly anisotropic layered compounds that have attracted growing interest from basic research to practical applications. Similar with MoS2, few-layer WS2 has remarkable physical properties. Here, we demonstrate for the first time that WS2 nanosheets exhibit ultrafast nonlinear saturable absorption property and high optical damage threshold. Soliton mode-locking operations are achieved separately in an erbium-doped fiber laser using two types of WS2-based saturable absorbers, one of which is fabricated by depositing WS2 nanosheets on a D-shaped fiber, while the other is synthesized by mixing WS2 solution with polyvinyl alcohol, and then evaporating them on a substrate. At the maximum pump power of 600 mW, two saturable absorbers can work stably at mode-locking state without damage, indicating that few-layer WS2 is a promising high-power flexible saturable absorber for ultrafast optics. Numerous applications may benefit from the ultrafast nonlinear features of WS2 nanosheets, such as high-power pulsed laser, materials processing, and frequency comb spectroscopy. PMID:25608729

Fabrication of WS2/GaN p-n Junction by Wafer-Scale WS2 Thin Film Transfer

PubMed Central

Yu, Yang; Fong, Patrick W. K.; Wang, Shifeng; Surya, Charles

2016-01-01

High quality wafer-scale free-standing WS2 grown by van der Waals rheotaxy (vdWR) using Ni as a texture promoting layer is reported. The microstructure of vdWR grown WS2 was significantly modified from mixture of crystallites with their c-axes both parallel to (type I) and perpendicular to (type II) the substrate to large type II crystallites. Wafer-scale transfer of vdWR grown WS2 onto different substrates by an etching-free technique was demonstrated for the first time that utilized the hydrophobic property of WS2 and hydrophilic property of sapphire. Our results show that vdWR is a reliable technique to obtain type-II textured crystallites in WS2, which is the key factor for the wafer-scale etching-free transfer. The transferred films were found to be free of observable wrinkles, cracks, or polymer residues. High quality p-n junctions fabricated by room-temperature transfer of the p-type WS2 onto an n-type GaN was demonstrated with a small leakage current density of 29.6 μA/cm2 at −1 V which shows superior performances compared to the directly grown WS2/GaN heterojunctions. PMID:27897210

Viewing social scenes: a visual scan-path study comparing fragile X syndrome and Williams syndrome.

PubMed

Williams, Tracey A; Porter, Melanie A; Langdon, Robyn

2013-08-01

Fragile X syndrome (FXS) and Williams syndrome (WS) are both genetic disorders which present with similar cognitive-behavioral problems, but distinct social phenotypes. Despite these social differences both syndromes display poor social relations which may result from abnormal social processing. This study aimed to manipulate the location of socially salient information within scenes to investigate the visual attentional mechanisms of: capture, disengagement, and/or general engagement. Findings revealed that individuals with FXS avoid social information presented centrally, at least initially. The WS findings, on the other hand, provided some evidence that difficulties with attentional disengagement, rather than attentional capture, may play a role in the WS social phenotype. These findings are discussed in relation to the distinct social phenotypes of these two disorders.

Fading-Figure Tracing in Williams Syndrome

ERIC Educational Resources Information Center

Nagai, Chiyoko; Inui, Toshio; Iwata, Makoto

2011-01-01

Williams syndrome (WS) is a neurodevelopmental disorder characterized by severe impairment of visuospatial abilities. Figure-drawing abilities, which are thought to reflect visuospatial abilities, have yet to be fully investigated in WS. The purpose of the present study was to clarify whether drawing abilities differ between WS individuals and…

Dysphagia caused by a lateral medullary infarction syndrome (Wallenberg's syndrome)

PubMed Central

El Mekkaoui, Amine; Irhoudane, Hanane; Ibrahimi, Adil; El Yousfi, Mounia

2012-01-01

A 68-year-old man was referred to our hospital for a dysphagia evolving for 10 days. Clinical examination had found neurological signs as contralateral Horner's syndrome, ipsilateral palatal paresis, gait ataxia and hoarseness. Video-fluoroscopy showed a lack of passage of contrast medium to the distal esophagus. Esogastroduodenoscopy was normal. The cranial MRI had shown an acute ischemic stroke in the left lateral medullar region and the diagnosis of Wallenberg syndrome (WS) was established. WS remains an unknown cause of dysphagia in the clinical practice of the gastroenterologist. PMID:23077713

7 CFR 1781.8 - Rates and terms-WS loans and WS advances and RCD loans.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., or from the installation on individual farms of land development or other soil and water improvements... principal benefits from the WS works of improvement or RCD measure being financed first become available. (3) The useful life of the WS works of improvement or RCD measure being financed with loan or advance...

Development of Verbal Passive in Williams Syndrome

ERIC Educational Resources Information Center

Perovic, Alexandra; Wexler, Kenneth

2010-01-01

Purpose: To experimentally investigate knowledge of passives of actional ("hold") and psychological ("love") verbs in children with Williams syndrome (WS). Passives are usually reported to be in line with mental age in WS. However, studies usually focus on passives of actional verbs only. Method: Twenty-six children with WS, ages 6-16, and 3…

7 CFR 1781.20 - Disbursement of WS and RCD loan funds and WS advance funds.

Code of Federal Regulations, 2010 CFR

2010-01-01

... each month to be reported to the Finance Office and charged to the borrower's account. This action will...: (1) When a future water supply is being developed with NRCS, WS advance funds, the NRCS State... sent immediately to the Finance Office and a copy provided for the processing office file. (3) When WS...

Comparing the broad socio-cognitive profile of youth with Williams syndrome and 22q11.2 deletion syndrome.

PubMed

Weisman, O; Feldman, R; Burg-Malki, M; Keren, M; Geva, R; Diesendruck, G; Gothelf, D

2017-12-01

Numerous studies have assessed the socio-cognitive profile in Williams syndrome (WS) and, independently, in 22q11.2 deletion syndrome (22q11.2DS). Yet, a cross-syndrome comparison of these abilities between individuals with these two syndromes with known social deficits has not been conducted. Eighty-two children participated in four study groups: WS (n = 18), 22q112.DS (n = 24), age-matched individuals with idiopathic developmental disability (IDD; n = 20) and typically developing (TD) controls (n = 20). Participants completed four socio-cognitive tests: facial emotion recognition, mental state attribution, differentiating real from apparent emotions and trait inference based on motives and actions-outcomes. The current findings demonstrate that children with WS were better in labelling happy faces compared with children with 22q11.2DS, partially reflecting their exaggerated social drive. In the false belief task, however, the WS and IDD groups performed poorly compared with the 22q11.2DS group, possibly due to their difficulty to interpret subtle social cues. When asked to identify the gap between real-negative vs. apparent-positive emotions, the 22q11.2DS group performed similarly to TD children but better than the WS group, possibly due to their anxious personality and their innate bias towards negatively valence cues. Finally, individuals with WS were more willing to become friends with a story character even when the character's motives were negative, reflecting their difficulty to avoid potentially harmful real-life situations. Overall, our multi-facet socio-cognitive battery uncovered strengths and weaknesses in social cognition that are syndrome-specific, shared among the genetic syndromes, or common to the three clinical groups compared with healthy controls. Our findings underscore the need to devise age-specific and condition-specific assessment tools and intervention programs towards improving these children's socio-cognitive deficits. © 2017

Association of Shah-Waardenburgh syndrome: a review of 6 cases.

PubMed

Jan, Iftikhar A; Stroedter, Lutz; Haq, Anwaar-ul; Din, Zaheer-ud

2008-04-01

Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. The aim of the article is to study the relative frequency of associations in 6 consecutive cases of SWS. A review of 6 consecutive patients with SWS was performed to study the frequency of various components of the syndrome. Six patients had features of SWS. All patients had HD; of these, 3 had rectosigmoid HD, whereas 3 had extended HD. All patients had white forelock of hairs with skin depigmentation. One patient had sensorineural deafness, whereas other babies were less than 1 year, and thus, full evaluation of hearing deficiency was not assessed. Three patients had blue eyes, whereas other babies had normal iris pigmentation. Skin depigmentation was noted in 5 of the 6 patients. Three babies were seriously malnourished and showed higher association of enterocolitis. Shah-Waardenburg syndrome is an uncommon association of HD. Depigmentation with a white forelock and skin manifestations are common, whereas blue iris, long segment disease, and enterocolitis are present in nearly half of the patients.

Hybrid chalcogenide nanoparticles: 2D-WS2 nanocrystals inside nested WS2 fullerenes.

PubMed

Hoshyargar, Faegheh; Corrales, Tomas P; Branscheid, Robert; Kolb, Ute; Kappl, Michael; Panthöfer, Martin; Tremel, Wolfgang

2013-10-28

The MOCVD assisted formation of nested WS2 inorganic fullerenes (IF-WS2) was performed by enhancing surface diffusion with iodine, and fullerene growth was monitored by taking TEM snapshots of intermediate products. The internal structure of the core-shell nanoparticles was studied using scanning electron microscopy (SEM) after cross-cutting with a focused ion beam (FIB). Lamellar reaction intermediates were found occluded in the fullerene particles. In contrast to carbon fullerenes, layered metal chalcogenides prefer the formation of planar, plate-like structures where the dangling bonds at the edges are stabilized by excess S atoms. The effects of the reaction and annealing temperatures on the composition and morphology of the final product were investigated, and the strength of the WS2 shell was measured by intermittent contact-mode AFM. The encapsulated lamellar structures inside the hollow spheres may lead to enhanced tribological activities.

Auditory cortical volumes and musical ability in Williams syndrome.

PubMed

Martens, Marilee A; Reutens, David C; Wilson, Sarah J

2010-07-01

Individuals with Williams syndrome (WS) have been shown to have atypical morphology in the auditory cortex, an area associated with aspects of musicality. Some individuals with WS have demonstrated specific musical abilities, despite intellectual delays. Primary auditory cortex and planum temporale volumes were manually segmented in 25 individuals with WS and 25 control participants, and the participants also underwent testing of musical abilities. Left and right planum temporale volumes were significantly larger in the participants with WS than in controls, with no significant difference noted between groups in planum temporale asymmetry or primary auditory cortical volumes. Left planum temporale volume was significantly increased in a subgroup of the participants with WS who demonstrated specific musical strengths, as compared to the remaining WS participants, and was highly correlated with scores on a musical task. These findings suggest that differences in musical ability within WS may be in part associated with variability in the left auditory cortical region, providing further evidence of cognitive and neuroanatomical heterogeneity within this syndrome. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Mother-Child Interaction as a Window to a Unique Social Phenotype in 22q11.2 Deletion Syndrome and in Williams Syndrome

ERIC Educational Resources Information Center

Weisman, Omri; Feldman, Ruth; Burg-Malki, Merav; Keren, Miri; Geva, Ronny; Diesendruck, Gil; Gothelf, Doron

2015-01-01

Mother-child interactions in 22q11.2 Deletion syndrome (22q11.2DS) and Williams syndrome (WS) were coded for maternal sensitivity/intrusiveness, child's expression of affect, levels of engagement, and dyadic reciprocity. WS children were found to express more positive emotions towards their mothers compared to 22q11.2DS children and those with…

Orientation Perception in Williams Syndrome: Discrimination and Integration

ERIC Educational Resources Information Center

Palomares, Melanie; Landau, Barbara; Egeth, Howard

2009-01-01

Williams Syndrome (WS) is a rare neurodevelopmental disorder, which stems from a genetic deletion on chromosome 7 and causes a profound weakness in visuospatial cognition. Our current study explores how orientation perception may contribute to the visuospatial deficits in WS. In Experiment 1, we found that WS individuals and normal 3-4 year olds…

Preparation and Characterization of WS2@SiO2 and WS2@PANI Core-Shell Nanocomposites

PubMed Central

Sade, Hagit

2018-01-01

Two tungsten disulfide (WS2)-based core-shell nanocomposites were fabricated using readily available reagents and simple procedures. The surface was pre-treated with a surfactant couple in a layer-by-layer approach, enabling good dispersion of the WS2 nanostructures in aqueous media and providing a template for the polymerization of a silica (SiO2) shell. After a Stöber-like reaction, a conformal silica coating was achieved. Inspired by the resulting nanocomposite, a second one was prepared by reacting the surfactant-modified WS2 nanostructures with aniline and an oxidizing agent in an aqueous medium. Here too, a conformal coating of polyaniline (PANI) was obtained, giving a WS2@PANI nanocomposite. Both nanocomposites were analyzed by electron microscopy, energy dispersive X-ray spectroscopy (EDS) and FTIR, verifying the core-shell structure and the character of shells. The silica shell was amorphous and mesoporous and the surface area of the composite increases with shell thickness. Polyaniline shells slightly differ in their morphologies dependent on the acid used in the polymerization process and are amorphous like the silica shell. Electron paramagnetic resonance (EPR) spectroscopy of the WS2@PANI nanocomposite showed variation between bulk PANI and the PANI shell. These two nanocomposites have great potential to expand the use of transition metals dichalcogenides (TMDCs) for new applications in different fields. PMID:29534426

Lung granulomatous response induced by infection with the intestinal nematode Nippostrongylusbrasiliensis is suppressed in mast cell-deficient Ws/Ws rats

PubMed Central

ARIZONO, N; NISHIDA, M; UCHIKAWA, R; YAMADA, M; MATSUDA, S; TEGOSHI, T; KITAMURA, Y; SASABE, M

1996-01-01

Certain nematode infections induce eosinophil infiltration and granulomatous responses in the lungs. To examine the role of mast cells in the development of lung lesions, normal +/+ and genetically mast cell-deficient Ws/Ws rats were infected with the nematode Nippostrongylusbrasiliensis. In +/+ rats, numbers of eosinophils in bronchoalveolar lavage fluid (BALF) increased significantly 3–7 days after infection, and granulomatous responses composed of histiocytes/macrophages and multinucleate giant cells were triggered in the lungs 3–14 days after infection. Challenge infection, which was carried out on day 28 after primary infection, induced much higher levels of granulomatous response than after primary infection, suggesting that the response is mediated at least in part by an immunological mechanism. In Ws/Ws rats, both the eosinophil percentage in BALF and the size of the granulomas in the lungs were significantly smaller than in +/+ rats after primary as well as after challenge infection. The amount of rat mast cell protease (RMCP) II in +/+ rat BALF was increased 1 day after primary infection and more significantly after challenge infection, suggesting that lung mucosal mast cells were activated more markedly after the challenge infection. In Ws/Ws rats, RMCP II was undetectable throughout the observation period. The time course of nematode migration in the lungs did not differ in +/+ and Ws/Ws rats. These results suggest that mast cell activation might be relevant to eosinophil infiltration and granulomatous response in the lungs, although the responses do not affect lung migration of the nematode. PMID:8870698

Beyond Behaviour: Is Social Anxiety Low in Williams Syndrome?

ERIC Educational Resources Information Center

Dodd, Helen F.; Schniering, Carolyn A.; Porter, Melanie A.

2009-01-01

Individuals with Williams syndrome (WS) exhibit striking social behaviour that may be indicative of abnormally low social anxiety. The present research aimed to determine whether social anxiety is unusually low in WS and to replicate previous findings of increased generalised anxiety in WS using both parent and self report. Fifteen individuals…

Social Phenotypes of Autism Spectrum Disorders and Williams Syndrome: Similarities and Differences

PubMed Central

Asada, Kosuke; Itakura, Shoji

2012-01-01

Autism spectrum disorders (ASD) and Williams syndrome (WS) both are neurodevelopmental disorders, each with a unique social phenotypic pattern. This review article aims to define the similarities and differences between the social phenotypes of ASD and WS. We review studies that have examined individuals with WS using diagnostic assessments such as the Autism Diagnostic Observation Schedule (ADOS), cross-syndrome direct comparison studies, and studies that have individually examined either disorder. We conclude that (1) individuals with these disorders show quite contrasting phenotypes for face processing (i.e., preference to faces and eyes) and sociability (i.e., interest in and motivation to interact with others), and (2) although the ADOS and a direct comparison study on pragmatic language ability suggest more deficits in ASD, individuals with WS are similarly impaired on social cognition and communicative skills. In light of these results, we discuss how cross-syndrome comparisons between ASD and WS can contribute to developmental theory, cognitive neuroscience, and the development and choice of clinical treatments. PMID:22866045

Anxiety Disorders in Williams Syndrome Contrasted with Intellectual Disability and the General Population: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Royston, R.; Howlin, P.; Waite, J.; Oliver, C.

2017-01-01

Individuals with specific genetic syndromes associated with intellectual disability (ID), such as Williams syndrome (WS), are at increased risk for developing anxiety disorders. A systematic literature review identified sixteen WS papers that could generate pooled prevalence estimates of anxiety disorders for WS. A meta-analysis compared these…

Standard weight (Ws) equations for four rare desert fishes

USGS Publications Warehouse

Didenko, A.V.; Bonar, Scott A.; Matter, W.J.

2004-01-01

Standard weight (Ws) equations have been used extensively to examine body condition in sport fishes. However, development of these equations for nongame fishes has only recently been emphasized. We used the regression-line-percentile technique to develop standard weight equations for four rare desert fishes: flannelmouth sucker Catostomus latipinnis, razorback sucker Xyrauchen texanus, roundtail chub Gila robusta, and humpback chub G. cypha. The Ws equation for flannelmouth suckers of 100-690 mm total length (TL) was developed from 17 populations: log10Ws = -5.180 + 3.068 log10TL. The Ws equation for razorback suckers of 110-885 mm TL was developed from 12 populations: log 10Ws = -4.886 + 2.985 log10TL. The W s equation for roundtail chub of 100-525 mm TL was developed from 20 populations: log10Ws = -5.065 + 3.015 log10TL. The Ws equation for humpback chub of 120-495 mm TL was developed from 9 populations: log10Ws = -5.278 + 3.096 log 10TL. These equations meet criteria for acceptable standard weight indexes and can be used to calculate relative weight, an index of body condition.

Tandem duplication within a Neurofibromatosis type I (NFI) gene exon in a family with features of Watson syndrome and Noonan syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tassabehji, M.; Strachan, T.; Colley, A.

Type 1 neurofibromatosis (NF1), Watson syndrome (WS), and Noonan syndrome (NS) show some overlap in clinical manifestations. In addition, WS has been shown to be linked to markers flanking the NF1 locus and a deletion at the NF1 locus demonstrated in a WS patient. This suggests either that WS and NF1 are allelic or the phenotypes arise from mutations in very closely linked genes. Here the authors provide evidence for the former by demonstrating a mutation in the NF1 gene in a family with features of both WS and NS. The mutation is an almost perfect in-frame tandem duplication ofmore » 42 bases in exon 28 of the NF1 gene. Unlike the mutations previously described in classical NF1, which show a preponderance of null alleles, the mutation in this family would be expected to result in a mutant neurofibromin product. 31 refs., 2 figs.« less

Theory of mind in Williams syndrome assessed using a nonverbal task.

PubMed

Porter, Melanie A; Coltheart, Max; Langdon, Robyn

2008-05-01

This study examined Theory of Mind in Williams syndrome (WS) and in normal chronological age-matched and mental age-matched control groups, using a picture sequencing task. This task assesses understanding of pretence, intention and false belief, while controlling for social-script knowledge and physical cause-and-effect reasoning. The task was selected because it is entirely non-verbal, so that the WS individuals could not rely on their good verbal skills when performing the task. Results indicated a specific deficit in understanding of false belief within the WS group. There was also evidence of heterogeneity in the WS group, with the false belief impairment restricted to only a particular subgroup of WS individuals identified originally by Porter, M., & Coltheart, M. (2005). Cognitive heterogeneity in Williams syndrome. Developmental Neuropsychology, 27(2), 275-306.

Social Attention, Joint Attention and Sustained Attention in Autism Spectrum Disorder and Williams Syndrome: Convergences and Divergences.

PubMed

Vivanti, Giacomo; Fanning, Peter A J; Hocking, Darren R; Sievers, Stephanie; Dissanayake, Cheryl

2017-06-01

There is limited knowledge on shared and syndrome-specific attentional profiles in autism spectrum disorder (ASD) and Williams syndrome (WS). Using eye-tracking, we examined attentional profiles of 35 preschoolers with ASD, 22 preschoolers with WS and 20 typically developing children across social and non-social dimensions of attention. Children with ASD and those with WS presented with overlapping deficits in spontaneous visual engagement with the target of others' attention and in sustained attention. Children with ASD showed syndrome-specific abnormalities in monitoring and following a person's referential gaze, as well as a lack of preferential attention to social stimuli. Children with ASD and WS present with shared as well as syndrome-specific abnormalities across social and non-social dimensions of attention.

Face processing in Williams syndrome is already atypical in infancy.

PubMed

D'Souza, Dean; Cole, Victoria; Farran, Emily K; Brown, Janice H; Humphreys, Kate; Howard, John; Rodic, Maja; Dekker, Tessa M; D'Souza, Hana; Karmiloff-Smith, Annette

2015-01-01

Face processing is a crucial socio-cognitive ability. Is it acquired progressively or does it constitute an innately-specified, face-processing module? The latter would be supported if some individuals with seriously impaired intelligence nonetheless showed intact face-processing abilities. Some theorists claim that Williams syndrome (WS) provides such evidence since, despite IQs in the 50s, adolescents/adults with WS score in the normal range on standardized face-processing tests. Others argue that atypical neural and cognitive processes underlie WS face-processing proficiencies. But what about infants with WS? Do they start with typical face-processing abilities, with atypicality developing later, or are atypicalities already evident in infancy? We used an infant familiarization/novelty design and compared infants with WS to typically developing controls as well as to a group of infants with Down syndrome matched on both mental and chronological age. Participants were familiarized with a schematic face, after which they saw a novel face in which either the features (eye shape) were changed or just the configuration of the original features. Configural changes were processed successfully by controls, but not by infants with WS who were only sensitive to featural changes and who showed syndrome-specific profiles different from infants with the other neurodevelopmental disorder. Our findings indicate that theorists can no longer use the case of WS to support claims that evolution has endowed the human brain with an independent face-processing module.

Williams syndrome and memory: a neuroanatomic and cognitive approach.

PubMed

Sampaio, Adriana; Sousa, Nuno; Férnandez, Montse; Vasconcelos, Cristiana; Shenton, Martha E; Gonçalves, Oscar F

2010-07-01

Williams Syndrome (WS) is described as displaying a dissociation within memory systems. As the integrity of hippocampal formation (HF) is determinant for memory performance, we examined HF volumes and its association with memory measures in a group of WS and in a typically development group. A significantly reduced intracranial content was found in WS, despite no differences were observed for HF absolute volumes between groups. When volumes were normalized, left HF was increased in WS. Moreover, a lack of the normal right > left HF asymmetry was observed in WS. No positive correlations were found between volumetric and neurocognitive data in WS. In sum, a relative enlargement of HF and atypical patterns of asymmetry suggest abnormal brain development in WS.

Examining Reports of Mental Health in Adults with Williams Syndrome

ERIC Educational Resources Information Center

Stinton, Chris; Tomlinson, Katie; Estes, Zachary

2012-01-01

Prior research suggests that individuals with Williams syndrome (WS) have a disposition towards anxiety. Information regarding this is typically derived from parents and carers. The perspectives of the individuals with WS are rarely included in research of this nature. We examined the mental health of 19 adults with WS using explicit (psychiatric…

Human versus Non-Human Face Processing: Evidence from Williams Syndrome

ERIC Educational Resources Information Center

Santos, Andreia; Rosset, Delphine; Deruelle, Christine

2009-01-01

Increased motivation towards social stimuli in Williams syndrome (WS) led us to hypothesize that a face's human status would have greater impact than face's orientation on WS' face processing abilities. Twenty-nine individuals with WS were asked to categorize facial emotion expressions in real, human cartoon and non-human cartoon faces presented…

Ambipolar behavior and thermoelectric properties of WS2 nanotubes

NASA Astrophysics Data System (ADS)

Yomogida, Yohei; Kawai, Hideki; Sugahara, Mitsunari; Okada, Ryotaro; Yanagi, Kazuhiro

WS2 nanotubes are rolled multi-walled nanotubes made by a layered material, tungsten disulfides Since the discovery by Tenne et al in 1992, various physical properties have been revealed. Theoretical studies have suggested their distinct electronic properties from those of two dimensional sheet, such as one-dimensional electronic strucutures with sharp van Hove singularities and chiralitiy depended electronic structures. Their fibril structures enable us to make their random network films, however, the films are not conducting, and thus have not been used for electronic applications. Here we demonstrate that carrier injections on the WS2 networks by an electrolyte gating approach could make the networks as a semiconducting channel. We clarified the Raman characteristics of WS2 nanotubes networks under electrolyte gating, and confirmed capability of electron and hole injections. We revealed ambipolar behaviors of the WS2 nanotube networks in field effect transistor setups with electrolyte gating. In additio, we demosntrate N-type and P-type control of thermoelectric properties of WS2 nanotubes by electrolyte gating.The power factor of the WS2 nanotubes almost approached to that of the single crystalline WS2 flakes, suggesting good potential for thermoelectric applications..

Attention to Faces in Williams Syndrome

ERIC Educational Resources Information Center

Riby, Deborah M.; Jones, Nicola; Brown, Philippa H.; Robinson, Lucy J.; Langton, Stephen R. H.; Bruce, Vicki; Riby, Leigh M.

2011-01-01

Williams syndrome (WS) is associated with distinct social behaviours. One component of the WS social phenotype is atypically prolonged face fixation. This behaviour co-exists with attention difficulties. Attention is multi-faceted and may impact on gaze behaviour in several ways. Four experiments assessed (i) attention capture by faces, (ii)…

Multi-walled carbon/IF-WS2 nanoparticles with improved thermal properties

NASA Astrophysics Data System (ADS)

Xu, Fang; Almeida, Trevor P.; Chang, Hong; Xia, Yongde; Wears, M. Lesley; Zhu, Yanqiu

2013-10-01

A unique new class of core-shell structured composite nanoparticles, C-coated inorganic fullerene-like WS2 (IF-WS2) hollow nanoparticles, has been created for the first time in large quantities, by a continuous chemical vapour deposition method using a rotary furnace. Transmission electron microscopy and Raman characterisations of the resulting samples reveal that the composite nanoparticles exhibited a uniform shell of carbon coating, ranging from 2-5 nm on the IF-WS2 core, with little or no agglomeration. Importantly, thermogravimetric analysis and differential scanning calorimetry analysis confirm that their thermal stability against oxidation in air has been improved by about 70 °C, compared to the pristine IF-WS2, making these new C-coated IF-WS2 nanoparticles more attractive for critical engineering applications.A unique new class of core-shell structured composite nanoparticles, C-coated inorganic fullerene-like WS2 (IF-WS2) hollow nanoparticles, has been created for the first time in large quantities, by a continuous chemical vapour deposition method using a rotary furnace. Transmission electron microscopy and Raman characterisations of the resulting samples reveal that the composite nanoparticles exhibited a uniform shell of carbon coating, ranging from 2-5 nm on the IF-WS2 core, with little or no agglomeration. Importantly, thermogravimetric analysis and differential scanning calorimetry analysis confirm that their thermal stability against oxidation in air has been improved by about 70 °C, compared to the pristine IF-WS2, making these new C-coated IF-WS2 nanoparticles more attractive for critical engineering applications. Electronic supplementary information (ESI) available: Sketch of the rotary furnace, XRD pattern comparison of IF-WS2 and 2H WS2, XRD patterns of C-coated IF-WS2 (41-50°), and TGA and MS curves for pristine IF-WS2. See DOI: 10.1039/c3nr03844k

Colour discrimination and categorisation in Williams syndrome.

PubMed

Farran, Emily K; Cranwell, Matthew B; Alvarez, James; Franklin, Anna

2013-10-01

Individuals with Williams syndrome (WS) present with impaired functioning of the dorsal visual stream relative to the ventral visual stream. As such, little attention has been given to ventral stream functions in WS. We investigated colour processing, a predominantly ventral stream function, for the first time in nineteen individuals with Williams syndrome. Colour discrimination was assessed using the Farnsworth-Munsell 100 hue test. Colour categorisation was assessed using a match-to-sample test and a colour naming task. A visual search task was also included as a measure of sensitivity to the size of perceptual colour difference. Results showed that individuals with WS have reduced colour discrimination relative to typically developing participants matched for chronological age; performance was commensurate with a typically developing group matched for non-verbal ability. In contrast, categorisation was typical in WS, although there was some evidence that sensitivity to the size of perceptual colour differences was reduced in this group. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genetic and Dynamic Analysis of Murine Peak Bone Density

DTIC Science & Technology

1998-10-01

number of diseases including Waardenburg syndrome (18, 19) and retinitis pigmentosa (20). Substantial computerized genetic data bases maintained at...411, 1992. 14. Foy, C., Newton, V., Wellesley, D., Harris, R., and Read, A. P. Assignment of the locus for Waardenburg syndrome type 1 to human...Balling, R., Gruss, P., and Strachan, T. Waardenburg’s syndrome patients have mutations in the human homologue of the Pax-3 paired box gene, Nature

Diurnal Cortisol Profile in Williams Syndrome in Novel and Familiar Settings

ERIC Educational Resources Information Center

Lense, Miriam Diane; Tomarken, Andrew J.; Dykens, Elisabeth M.

2013-01-01

Williams syndrome (WS) is a neurodevelopmental genetic disorder associated with high rates of anxiety and social issues. We examined diurnal cortisol, a biomarker of the stress response, in adults with WS in novel and familiar settings, and compared these profiles to typically developing (TD) adults. WS and TD participants had similar profiles in…

Photosynthetic acclimation of WS and WS-gpt2 in Arabidopsis thaliana under fluctuating natural light condition

NASA Astrophysics Data System (ADS)

Pa'ee, Furzani; Johnson, Giles

2017-10-01

Photoacclimation is a process by which photosynthetic capacity is regulated in response to environmental adjustments in terms of light regime. Photoacclimation is essential in determining the photosynthetic capacity to optimize light use and to avoid potentially damaging effects. Previous work in our laboratory has identified a gene, gpt2 (At1g61800) that is essential for plants to acclimate to an increase and decrease of growth irradiance, separately. To investigate the photoacclimation ability towards fluctuating natural light condition in Arabidopsis thaliana, photosynthetic capacity was measured in plants of the accession Wassileskija (WS) and in plants lacking expression of the gene At1g61800 (WS-gpt2). The experiment was carried out over a time span from early Autumn to early Spring season in 2010-2011 and 2011-2012. The seedlings were grown in an unheated greenhouse in Manchester, UK without supplementary lighting. Gas exchange measurements and chlorophyll content estimation were performed on WS and WS-gpt2 and it showed that both sets of plants were able to acclimate to fluctuating natural light condition. Therefore, it is suggested that the mechanisms of acclimation in a separate growth light condition is mechanistically distinct than the mechanism under fluctuating natural light condition.

Attention in Williams Syndrome and Down's Syndrome: Performance on the New Early Childhood Attention Battery

ERIC Educational Resources Information Center

Breckenridge, Kate; Braddick, Oliver; Anker, Shirley; Woodhouse, Margaret; Atkinson, Janette

2013-01-01

Attentional problems are commonly reported as a feature of the behavioural profile in both Williams syndrome (WS) and Down's syndrome (DS). Recent studies have begun to investigate these impairments empirically, acknowledging the need for an approach that considers cross-syndrome comparisons and developmental changes across the different component…

Viewing Social Scenes: A Visual Scan-Path Study Comparing Fragile X Syndrome and Williams Syndrome

ERIC Educational Resources Information Center

Williams, Tracey A.; Porter, Melanie A.; Langdon, Robyn

2013-01-01

Fragile X syndrome (FXS) and Williams syndrome (WS) are both genetic disorders which present with similar cognitive-behavioral problems, but distinct social phenotypes. Despite these social differences both syndromes display poor social relations which may result from abnormal social processing. This study aimed to manipulate the location of…

Attribution of Negative Intention in Williams Syndrome

ERIC Educational Resources Information Center

Godbee, Kali; Porter, Melanie A.

2013-01-01

People with Williams syndrome (WS) are said to have sociable and extremely trusting personalities, approaching strangers without hesitation. This study investigated whether people with WS are less likely than controls to attribute negative intent to others when interpreting a series of ambiguous pictures. This may, at least partially, explain…

Executive Function in Williams and Down Syndromes

ERIC Educational Resources Information Center

Carney, Daniel P. J.; Brown, Janice H.; Henry, Lucy A.

2013-01-01

Williams (WS) and Down (DS) syndromes are characterised by roughly opposing ability profiles. Relative verbal strengths and visuospatial difficulties have been reported in those with WS, while expressive language difficulties have been observed in individuals with DS. Few investigations into the executive function (EF) skills of these groups have…

Understanding Williams Syndrome: Behavioral Patterns and Interventions.

ERIC Educational Resources Information Center

Semel, Eleanor; Rosner, Sue R.

This guide to Williams syndrome (WS), a congenital disorder characterized by developmental/cognitive limitations but relatively high verbal and social skills, explains the strengths, difficulties and variations found among individuals with the condition and offers guidelines for intervention in the unusual properties of the WS behavioral profile.…

Patterns and Trajectories in Williams Syndrome: The Case of Visual Orientation Discrimination

ERIC Educational Resources Information Center

Palomares, Melanie; Englund, Julia A.; Ahlers, Stephanie

2011-01-01

Williams Syndrome (WS) is a developmental disorder typified by deficits in visuospatial cognition. To understand the nature of this deficit, we characterized how people with WS perceive visual orientation, a fundamental ability related to object identification. We compared WS participants to typically developing children (3-6 years of age) and…

Description of common musculoskeletal findings in Williams Syndrome and implications for therapies.

PubMed

Copes, L E; Pober, B R; Terilli, C A

2016-07-01

Williams syndrome (WS), also referred to as Williams-Beuren syndrome (WBS), is a relatively rare genetic disorder affecting ∼1/10,000 persons. Since the disorder is caused by a micro-deletion of ∼1.5 Mb, it is not surprising that the manifestations of WS are extremely broad, involving most body systems. In this paper, we primarily focus on the musculoskeletal aspects of WS as these findings have not been the subject of a comprehensive review. We review the MSK features commonly seen in individuals with WS, along with related sensory and neurological issues interacting with and compounding underlying MSK abnormalities. We end by providing perspective, particularly from the vantage point of a physical therapist, on therapeutic interventions to address the most common MSK and related features seen in WS. Clin. Anat. 29:578-589, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Proposed standard-weight (W(s)) equations for kokanee, golden trout and bull trout

USGS Publications Warehouse

Hyatt, M.H.; Hubert, W.A.

2000-01-01

We developed standard-weight (W(s)) equations for kokanee (lacustrine Oncorhynchus nerka), golden trout (O. aguabonita), and bull trout (Salvelinus confluentus) using the regression-line-percentile technique. The W(s) equation for kokanee of 120-550 mm TL is log10 W(s) = -5.062 + 3.033 log10 TL, when W(s) is in grams and TL is total length in millimeters; the English-unit equivalent is log10 W(s) = -3.458 + 3.033 log10 TL, when W(s) is in pounds and TL is total length in inches. The W(s) equation for golden trout of 120-530 mm TL is log10 W(s) = -5.088 + 3.041 log10 TL, with the English-unit equivalent being log10 W(s) = -3.473 + 3.041 log10 TL. The W(s) equation for bull trout of 120-850 mm TL is log10 W(s) = -5.327 + 3.115 log10 TL, with the English-unit equivalent being log10 W(s) = -3.608 + 3.115 log10 TL.

Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10.

PubMed

Pingault, Veronique; Pierre-Louis, Laurence; Chaoui, Asma; Verloes, Alain; Sarrazin, Elisabeth; Brandberg, Goran; Bondurand, Nadege; Uldall, Peter; Manouvrier-Hanu, Sylvie

2014-09-01

Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype-phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype-phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS. © 2014 Wiley Periodicals, Inc.

Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10

PubMed Central

Pingault, Veronique; Pierre-Louis, Laurence; Chaoui, Asma; Verloes, Alain; Sarrazin, Elisabeth; Brandberg, Goran; Bondurand, Nadege; Uldall, Peter; Manouvrier-Hanu, Sylvie

2014-01-01

Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype-phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype-phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS. PMID:24845202

Developmental delays in phonological recoding among children and adolescents with Down syndrome and Williams syndrome.

PubMed

Danielsson, Henrik; Henry, Lucy; Messer, David; Carney, Daniel P J; Rönnberg, Jerker

2016-08-01

This study examined the development of phonological recoding in short-term memory (STM) span tasks among two clinical groups with contrasting STM and language profiles: those with Down syndrome (DS) and Williams syndrome (WS). Phonological recoding was assessed by comparing: (1) performance on phonologically similar and dissimilar items (phonological similarity effects, PSE); and (2) items with short and long names (word length effects, WLE). Participant groups included children and adolescents with DS (n=29), WS (n=25) and typical development (n=51), all with average mental ages around 6 years. The group with WS, contrary to predictions based on their relatively strong verbal STM and language abilities, showed no evidence for phonological recoding. Those in the group with DS, with weaker verbal STM and language abilities, showed positive evidence for phonological recoding (PSE), but to a lesser degree than the typical group (who showed PSE and WLE). These findings provide new information about the memory systems of these groups of children and adolescents, and suggest that STM processes involving phonological recoding do not fit with the usual expectations of the abilities of children and adolescents with WS and DS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tunable Wetting Property in Growth Mode-Controlled WS2 Thin Films

NASA Astrophysics Data System (ADS)

Choi, Byoung Ki; Lee, In Hak; Kim, Jiho; Chang, Young Jun

2017-04-01

We report on a thickness-dependent wetting property of WS2/Al2O3 and WS2/SiO2/Si structures. We prepared WS2 films with gradient thickness by annealing thickness-controlled WO3 films at 800 °C in sulfur atmosphere. Raman spectroscopy measurements showed step-like variation in the thickness of WS2 over substrates several centimeters in dimension. On fresh surfaces, we observed a significant change in the water contact angle depending on film thickness and substrate. Transmission electron microscopy analysis showed that differences in the surface roughness of WS2 films can account for the contrasting wetting properties between WS2/Al2O3 and WS2/SiO2/Si. The thickness dependence of water contact angle persisted for longer than 2 weeks, which demonstrates the stability of these wetting properties when exposed to air contamination.

Ultra-toughened nylon 12 nanocomposites reinforced with IF-WS2.

PubMed

Xu, Fang; Yan, Chunze; Shyng, Yat-Tarng; Chang, Hong; Xia, Yongde; Zhu, Yanqiu

2014-08-15

Inorganic fullerene-like WS2 nanoparticle- (IF-WS2) reinforced nylon 12 nanocomposites have been prepared through effective ultrasonic mixing without using any surfactant, followed by molding at 220 °C. Morphological characterizations using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and microcomputed tomography (micro-CT) have revealed the excellent dispersion of IF-WS2 nanoparticles in the nylon 12 matrix. X-ray diffraction (XRD) analyses have confirmed that a phase transition from α'-phase to a more stable γ-phase took place during the sintering of nylon 12, regardless of the amount of IF-WS2 added to the matrix. At a very low IF-WS2 content of 2 wt%, the tensile strength and bending strength of the composites increased slightly by 27% and 28%, respectively. However, the toughness dramatically improved by 185% and 148% at IF-WS2 additions of 0.25 and 0.5 wt%, respectively, when compared to the neat nylon 12. It is believed that such improvements should mainly be attributed to the well-dispersed IF-WS2 within the matrix. The vastly improved toughness suggests that the resulting polymer nanocomposites could be promising for structural and high-performance impact applications.

Ultra-toughened nylon 12 nanocomposites reinforced with IF-WS2

NASA Astrophysics Data System (ADS)

Xu, Fang; Yan, Chunze; Shyng, Yat-Tarng; Chang, Hong; Xia, Yongde; Zhu, Yanqiu

2014-08-01

Inorganic fullerene-like WS2 nanoparticle- (IF-WS2) reinforced nylon 12 nanocomposites have been prepared through effective ultrasonic mixing without using any surfactant, followed by molding at 220 °C. Morphological characterizations using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and microcomputed tomography (micro-CT) have revealed the excellent dispersion of IF-WS2 nanoparticles in the nylon 12 matrix. X-ray diffraction (XRD) analyses have confirmed that a phase transition from α‧-phase to a more stable γ-phase took place during the sintering of nylon 12, regardless of the amount of IF-WS2 added to the matrix. At a very low IF-WS2 content of 2 wt%, the tensile strength and bending strength of the composites increased slightly by 27% and 28%, respectively. However, the toughness dramatically improved by 185% and 148% at IF-WS2 additions of 0.25 and 0.5 wt%, respectively, when compared to the neat nylon 12. It is believed that such improvements should mainly be attributed to the well-dispersed IF-WS2 within the matrix. The vastly improved toughness suggests that the resulting polymer nanocomposites could be promising for structural and high-performance impact applications.

Superior Field Emission Properties of Layered WS2-RGO Nanocomposites

PubMed Central

Rout, Chandra Sekhar; Joshi, Padmashree D.; Kashid, Ranjit V.; Joag, Dilip S.; More, Mahendra A.; Simbeck, Adam J.; Washington, Morris; Nayak, Saroj K.; Late, Dattatray J.

2013-01-01

We report here the field emission studies of a layered WS2-RGO composite at the base pressure of ~1 × 10−8 mbar. The turn on field required to draw a field emission current density of 1 μA/cm2 is found to be 3.5, 2.3 and 2 V/μm for WS2, RGO and the WS2-RGO composite respectively. The enhanced field emission behavior observed for the WS2-RGO nanocomposite is attributed to a high field enhancement factor of 2978, which is associated with the surface protrusions of the single-to-few layer thick sheets of the nanocomposite. The highest current density of ~800 μA/cm2 is drawn at an applied field of 4.1 V/μm from a few layers of the WS2-RGO nanocomposite. Furthermore, first-principles density functional calculations suggest that the enhanced field emission may also be due to an overalp of the electronic structures of WS2 and RGO, where graphene-like states are dumped in the region of the WS2 fundamental gap. PMID:24257504

Phonon shift in chemically exfoliated WS2 nanosheet

NASA Astrophysics Data System (ADS)

Sarkar, Abdus Salam; Pal, Suman Kalyan

2018-04-01

We have synthesized few layer WS2 nanosheets in a low boiling point solvent. Few layer of WS2 sheets are characterized by various techniques such as UV-visible and Raman spectroscopy, transmission electron microscopy (TEM), atomic force microscopy (AFM) and scanning electron microscopy (SEM). UV-Vis absorption spectra confirm the well dispersed in isopropyl alcohol. SEM and TEM images indicate the sheet like morphology of WS2. Atomic force microscopy image and room temperature Raman spectroscopy confirm the exfoliation of few layer (4-5 layer) of WS2. Further, Raman spectroscopy was used as a meteorology tool to determine the temperature co-efficient. We have systematically investigated the temperature dependent Raman spectroscopic behavior of few layer WS2. Our results depict the softening of the Raman modes E12g in plane vibration and A1g out of plane vibration with increasing the temperature from 77 K to 300 K. Softening of the Raman modes could be explained in terms of the double resonance which is active in the layered materials. The observed temperature coefficients for two Raman peaks E12g and A1g, are - 0.022 cm-1 and -0.009 cm-1, respectively.

Compare Of the West Syndrome with Other Syndromes in the Epileptic Encephalopathy - Kosovo Experience

PubMed Central

Zeka, Naim; Gërguri, Abdurrahim; Bejiqi, Ramush; Retkoceri, Ragip; Vuciterna, Armend

2017-01-01

BACKGROUND: West Syndrome (WS) represents as a specific epileptic encephalopathy characterised with a unique type of attacks, called infantile spasms, severe forms of abnormalities in electroencephalographic (EEG) records as a hypsarythmias and delays in the psychomotoric development. The characteristics of the disease, mostly affecting male gender, are infantile spasms and typical findings in EEG as a hypsarythmia. Infantile spasms are a consequence of many factors in the undeveloped brain. AIM: We aimed: (1) to see the incidence of the illness and the spreading out because of gender in rapport with other syndromes in the epileptic encephalopathies group; (2) to show principles of the treatment for the illness; and (3) to present the effects of the disease in the psycho-motoric development of affected children. METHODS: The study was designed as a cross-sectional study of the patients with epileptic encephalopathies, treated in Paediatric Clinic in Prishtina, from 1st of January 2013 until the 31st of December 2015. RESULTS: From the cohort group of 97 children diagnosed with epileptic encephalopathies, in 14 of them clinical and EEG signs of WS were noted. The earliest age of disease manifestation was 74 days (± 63.8 days). On the group of children with WS, 13 of them with Natrium Valpropat were treated, with the doses of 301.9 mg (± 64.1). From the cohort group, in 89 children (91.8%) psychomotoric retardation was documented, within the higher reoccurrence in the undifferentiated epileptic encephalopathies (96%) and the WS (78.6%). CONCLUSION: WS is a frequent disease of the encephalopathies with the epileptogenic framework. The resistance in anticonvulsive therapy is huge, and psychomotoric retardation follows a big percentage of children with this syndrome. PMID:29362620

Attention Bias to Emotional Faces Varies by IQ and Anxiety in Williams Syndrome

ERIC Educational Resources Information Center

McGrath, Lauren M.; Oates, Joyce M.; Dai, Yael G.; Dodd, Helen F.; Waxler, Jessica; Clements, Caitlin C.; Weill, Sydney; Hoffnagle, Alison; Anderson, Erin; MacRae, Rebecca; Mullett, Jennifer; McDougle, Christopher J.; Pober, Barbara R.; Smoller, Jordan W.

2016-01-01

Individuals with Williams syndrome (WS) often experience significant anxiety. A promising approach to anxiety intervention has emerged from cognitive studies of attention bias to threat. To investigate the utility of this intervention in WS, this study examined attention bias to happy and angry faces in individuals with WS (N = 46). Results showed…

A de novo 2q35-q36.1 deletion incorporating IHH in a Chinese boy (47,XYY) with syndactyly, type III Waardenburg syndrome, and congenital heart disease.

PubMed

Wang, D; Ren, G F; Zhang, H Z; Yi, C Y; Peng, Z J

2016-12-02

Reports of terminal and interstitial deletions of the long arm of chromosome 2 are rare in the literature. Here, we present a case report concerning a Chinese boy with a 47,XYY karyotype and a de novo deletion comprising approximately 5 Mb between 2q35 and q36.1, along with syndactyly, type III Waardenburg syndrome, and congenital heart disease. High-resolution chromosome analysis to detect copy number variations was carried out using an Affymetrix microarray platform, and the genes affected by the patient's deletion, including IHH, were determined. However, no copy number changes were observed in his healthy parents. The present case exhibited novel syndactyly features, broadening the spectrum of clinical findings observed in individuals with 2q interstitial deletions. Our data, together with previous observations, suggest that IHH haploinsufficiency is the principal pathogenic factor in the syndactyly phenotype in this study, and that different types of variations at the IHH locus may cause divergent disease phenotypes. This is the first report of the involvement of IHH haploinsufficiency in syndactyly phenotype.

Comparing the Broad Socio-Cognitive Profile of Youth with Williams Syndrome and 22Q11.2 Deletion Syndrome

ERIC Educational Resources Information Center

Weisman, O.; Feldman, R.; Burg-Malki, M.; Keren, M.; Geva, R.; Diesendruck, G.; Gothelf, D.

2017-01-01

Background: Numerous studies have assessed the socio-cognitive profile in Williams syndrome (WS) and, independently, in 22q11.2 deletion syndrome (22q11.2DS). Yet, a cross-syndrome comparison of these abilities between individuals with these two syndromes with known social deficits has not been conducted. Methods: Eighty-two children participated…

Williams Syndrome: A Relationship between Genetics, Brain Morphology and Behaviour

ERIC Educational Resources Information Center

Fahim, C.; Yoon, U.; Nashaat, N. H.; Khalil, A. K.; El-Belbesy, M.; Mancini-Marie, A.; Evans, A. C.; Meguid, N.

2012-01-01

Background: Genetically Williams syndrome (WS) promises to provide essential insight into the pathophysiology of cortical development because its ~28 deleted genes are crucial for cortical neuronal migration and maturation. Phenotypically, WS is one of the most puzzling childhood neurodevelopmental disorders affecting most intellectual…

Psycholinguistic Abilities of Children with Williams Syndrome

ERIC Educational Resources Information Center

Rossi, Natalia F.; Heinze, Elena Garayzabal; Giacheti, Celia M.; Goncalves, Oscar F.; Sampaio, Adriana

2012-01-01

The objective of this study was to investigate the psycholinguistic abilities of children with Williams syndrome (WS) and typically developing children using the Illinois Test of Psycholinguistic Abilities (ITPA). Performance on the ITPA was analysed in a group with WS (N=20, mean age=8.5 years, SD=1.62) and two typically developing groups,…

POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome

PubMed Central

Lessel, Davor; Hisama, Fuki M.; Szakszon, Katalin; Saha, Bidisha; Sanjuanelo, Alexander Barrios; Salbert, Bonnie A.; Steele, Pamela D.; Baldwin, Jennifer; Brown, W. Ted; Piussan, Charles; Plauchu, Henri; Szilvássy, Judit; Horkay, Edit; Hoögel, Josef; Martin, George M.; Herr, Alan J.; Oshima, Junko; Kubisch, Christian

2015-01-01

Segmental progeroid syndromes are rare, heterogeneous disorders characterized by signs of premature aging affecting more than one tissue or organ. A prototypic example is the Werner syndrome (WS), caused by biallelic germline mutations in the Werner helicase gene (WRN). While heterozygous lamin A/C (LMNA) mutations are found in a few nonclassical cases of WS, another 10%–15% of patients initially diagnosed with WS do not have mutations in WRN or LMNA. Germline POLD1 mutations were recently reported in five patients with another segmental progeroid disorder: mandibular hypoplasia, deafness, progeroid features syndrome. Here, we describe eight additional patients with heterozygous POLD1 mutations, thereby substantially expanding the characterization of this new example of segmental progeroid disorders. First, we identified POLD1 mutations in patients initially diagnosed with WS. Second, we describe POLD1 mutation carriers without clinically relevant hearing impairment or mandibular underdevelopment, both previously thought to represent obligate diagnostic features. These patients also exhibit a lower incidence of metabolic abnormalities and joint contractures. Third, we document postnatal short stature and premature greying/loss of hair in POLD1 mutation carriers. We conclude that POLD1 germline mutations can result in a variably expressed and probably underdiagnosed segmental progeroid syndrome. PMID:26172944

Dissociation of spatial memory systems in Williams syndrome.

PubMed

Bostelmann, Mathilde; Fragnière, Emilie; Costanzo, Floriana; Di Vara, Silvia; Menghini, Deny; Vicari, Stefano; Lavenex, Pierre; Lavenex, Pamela Banta

2017-11-01

Williams syndrome (WS), a genetic deletion syndrome, is characterized by severe visuospatial deficits affecting performance on both tabletop spatial tasks and on tasks which assess orientation and navigation. Nevertheless, previous studies of WS spatial capacities have ignored the fact that two different spatial memory systems are believed to contribute parallel spatial representations supporting navigation. The place learning system depends on the hippocampal formation and creates flexible relational representations of the environment, also known as cognitive maps. The spatial response learning system depends on the striatum and creates fixed stimulus-response representations, also known as habits. Indeed, no study assessing WS spatial competence has used tasks which selectively target these two spatial memory systems. Here, we report that individuals with WS exhibit a dissociation in their spatial abilities subserved by these two memory systems. As compared to typically developing (TD) children in the same mental age range, place learning performance was impaired in individuals with WS. In contrast, their spatial response learning performance was facilitated. Our findings in individuals with WS and TD children suggest that place learning and response learning interact competitively to control the behavioral strategies normally used to support human spatial navigation. Our findings further suggest that the neural pathways supporting place learning may be affected by the genetic deletion that characterizes WS, whereas those supporting response learning may be relatively preserved. The dissociation observed between these two spatial memory systems provides a coherent theoretical framework to characterize the spatial abilities of individuals with WS, and may lead to the development of new learning strategies based on their facilitated response learning abilities. © 2017 Wiley Periodicals, Inc.

Association between Speech-Language, General Cognitive Functioning and Behaviour Problems in Individuals with Williams Syndrome

ERIC Educational Resources Information Center

Rossi, N. F.; Giacheti, C. M.

2017-01-01

Background: Williams syndrome (WS) phenotype is described as unique and intriguing. The aim of this study was to investigate the associations between speech-language abilities, general cognitive functioning and behavioural problems in individuals with WS, considering age effects and speech-language characteristics of WS sub-groups. Methods: The…

Visually Guided Step Descent in Children with Williams Syndrome

ERIC Educational Resources Information Center

Cowie, Dorothy; Braddick, Oliver; Atkinson, Janette

2012-01-01

Individuals with Williams syndrome (WS) have impairments in visuospatial tasks and in manual visuomotor control, consistent with parietal and cerebellar abnormalities. Here we examined whether individuals with WS also have difficulties in visually controlling whole-body movements. We investigated visual control of stepping down at a change of…

Gender attribution and gender agreement in French Williams syndrome.

PubMed

Boloh, Yves; Ibernon, Laure; Royer, Stéphanie; Escudier, Frédérique; Danillon, Aurélia

2009-01-01

Previous studies on grammatical gender in French individuals with Williams syndrome (WS) have led to conflicting findings and interpretations regarding keys abilities--gender attribution and gender agreement. New production data from a larger WS sample (N=24) showed that gender attribution scores in WS participants exactly mirrored those of controls: all groups overwhelmingly relied on the masculine as the default gender. WS participants' agreement scores were far lower than those of CA-controls though not significantly below those of MA-controls. They also did not improve with age, which might suggest a permanent disability in this area.

Social Attention, Joint Attention and Sustained Attention in Autism Spectrum Disorder and Williams Syndrome: Convergences and Divergences

ERIC Educational Resources Information Center

Vivanti, Giacomo; Fanning, Peter A. J.; Hocking, Darren R.; Sievers, Stephanie; Dissanayake, Cheryl

2017-01-01

There is limited knowledge on shared and syndrome-specific attentional profiles in autism spectrum disorder (ASD) and Williams syndrome (WS). Using eye-tracking, we examined attentional profiles of 35 preschoolers with ASD, 22 preschoolers with WS and 20 typically developing children across social and non-social dimensions of attention. Children…

Nuclear magnetic resonance study of fullerene-like WS2.

PubMed

Panich, A M; Kopnov, F; Tenne, R

2006-06-01

Inorganic fullerene-like nanoparticles of WS2 (IF-WS2), are synthesized by a reaction of tungsten oxide with molecular hydrogen and hydrogen sulfide. The synthesized nanoparticles appear as large agglomerates (>40 microns), each one counting thousands of IF nanoparticles. 1H nuclear magnetic resonance study of these nanoparticles is reported. The measurements show that the prepared product contains water (and possibly some hydrogen) molecules that occupy the voids in the central part of the fullerene-like nanoparticles and the nanopores between the adhering IF-WS2 particles. Defects in the IF-WS2 structure, arising due to the strain release during the folding of the layers, may result in additional sites for the absorbed water. Vacuum annealing of the powder leads to substantial reduction in the amount of absorbed water molecules.

Musicality Correlates with Sociability and Emotionality in Williams Syndrome

ERIC Educational Resources Information Center

Ng, Rowena; Lai, Philip; Levitin, Daniel J.; Bellugi, Ursula

2013-01-01

Williams syndrome (WS) is a neurogenetic developmental disorder characterized by peaks and valleys of cognitive abilities. One peak that has been understudied is the affinity that many individuals with WS have with music. It remains unknown whether their high levels of musical interest, skill, and expressivity are related to their sociable…

Atypical Sleep Architecture and Altered EEG Spectra in Williams Syndrome

ERIC Educational Resources Information Center

Gombos, F.; Bodizs, R.; Kovacs, I.

2011-01-01

Background: Williams syndrome (WS) is a neurodevelopmental genetic disorder characterised by physical abnormalities and a distinctive cognitive profile with intellectual disabilities (IDs) and learning difficulties. Methods: In our study, nine adolescents and young adults with WS and 9 age- and sex-matched typically developing (TD) participants…

Addressing social skills deficits in adults with Williams syndrome.

PubMed

Fisher, Marisa H; Morin, Lindsay

2017-12-01

Individuals with Williams syndrome (WS) are hypersocial; yet, they experience social difficulties and trouble with relationships. This report summarizes findings from three studies examining the social functioning of adults with WS and the feasibility of a social skills training program for adults with WS (SSTP-WS) through the examination of performance on initial lesson plans. Study 1: 114 parents of adults with WS completed the Social Responsiveness Scale-2. Study 2: 10 adults with WS and 12 of their parents participated in focus groups to further describe the deficits identified in Study 1 and to discuss a SSTP-WS. Study 3: 30 adults with WS were randomly assigned to 2 lessons on either conversations or relationships and pre-post change in social skills knowledge was assessed. Study 1 indicates adults with WS experience severe social impairments in social cognition, and mild-moderate impairments in social awareness and social communication. Qualitative results in Study 2 indicate a SSTP-WS should address conversation skills and relationships. In Study 3, participants showed gains in social skills knowledge following completion of lessons. A SSTP-WS may be beneficial for adults with WS. Future research should describe the social needs of individuals with WS at different ages and should further develop a SSTP-WS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Accelerated epigenetic aging in Werner syndrome.

PubMed

Maierhofer, Anna; Flunkert, Julia; Oshima, Junko; Martin, George M; Haaf, Thomas; Horvath, Steve

2017-04-01

Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0.0072) and intrinsic epigenetic age acceleration (p=0.04), the latter of which is independent of age-related changes in the composition of peripheral blood cells. A multivariate model analysis reveals that WS is associated with an increase in DNA methylation age (on average 6.4 years, p=0.011) even after adjusting for chronological age, gender, and blood cell counts. Further, WS might be associated with a reduction in naïve CD8+ T cells (p=0.025) according to imputed measures of blood cell counts. Overall, this study shows that WS is associated with an increased epigenetic age of blood cells which is independent of changes in blood cell composition. The extent to which this alteration is a cause or effect of WS disease phenotypes remains unknown.

Explorative Function in Williams Syndrome Analyzed through a Large-Scale Task with Multiple Rewards

ERIC Educational Resources Information Center

Foti, F.; Petrosini, L.; Cutuli, D.; Menghini, D.; Chiarotti, F.; Vicari, S.; Mandolesi, L.

2011-01-01

This study aimed to evaluate spatial function in subjects with Williams syndrome (WS) by using a large-scale task with multiple rewards and comparing the spatial abilities of WS subjects with those of mental age-matched control children. In the present spatial task, WS participants had to explore an open space to search nine rewards placed in…

Effect of 2D WS2 Addition on Cold-Sprayed Aluminum Coating

NASA Astrophysics Data System (ADS)

Loganathan, Archana; Rengifo, Sara; Hernandez, Alexander Franco; Emirov, Yusuf; Zhang, Cheng; Boesl, Benjamin; Karthikeyan, Jeganathan; Agarwal, Arvind

2017-10-01

Tungsten disulfide (WS2) has excellent solid lubrication properties due to its 2D layered structure. This study focuses on depositing Al-2 wt.% WS2 composite coating by cold spray technique. The effect of WS2 addition on the microstructure, mechanical and tribological properties of the composite coatings is examined in the as-deposited and heat-treated conditions. After heat treatment, the coating density increased to 99% with improved intersplat bonding. The microhardness of the heat-treated Al-2 wt.% WS2 coating increased by 56% as compared to the as-sprayed coating. The wear resistance of heat-treated Al-2 wt.% WS2 coating improved by 75% with a synergistic reduction in the coefficient of friction (COF) by 51%. Transmission electron microscopy investigation reveals the presence of layered WS2 within aluminum splats with a strong interface. This study shows that cold spraying can be effectively used to integrate 2D layered WS2 as a solid lubricant in the metallic coatings.

An Investigation into Semantic and Phonological Processing in Individuals with Williams Syndrome

ERIC Educational Resources Information Center

Lee, Cheryl S.; Binder, Katherine S.

2014-01-01

Purpose: The current study examined semantic and phonological processing in individuals with Williams syndrome (WS). Previous research in language processing in individuals with WS suggests a complex linguistic system characterized by "deviant" semantic organization and differential phonological processing. Method: Two experiments…

Williams Syndrome and Memory: A Neuroanatomic and Cognitive Approach

ERIC Educational Resources Information Center

Sampaio, Adriana; Sousa, Nuno; Fernandez, Montse; Vasconcelos, Cristiana; Shenton, Martha E.; Goncalves, Oscar F.

2010-01-01

Williams Syndrome (WS) is described as displaying a dissociation within memory systems. As the integrity of hippocampal formation (HF) is determinant for memory performance, we examined HF volumes and its association with memory measures in a group of WS and in a typically development group. A significantly reduced intracranial content was found…

The Interplay between Anxiety and Social Functioning in Williams Syndrome

ERIC Educational Resources Information Center

Riby, Deborah M.; Hanley, Mary; Kirk, Hannah; Clark, Fiona; Little, Katie; Fleck, Ruth; Janes, Emily; Kelso, Linzi; O'Kane, Fionnuala; Cole-Fletcher, Rachel; Allday, Marianne Hvistendahl; Hocking, Darren; Cornish, Kim; Rodgers, Jacqui

2014-01-01

The developmental disorder Williams syndrome (WS) has been associated with an atypical social profile of hyper-sociability and heightened social sensitivity across the developmental spectrum. In addition, previous research suggests that both children and adults with WS have a predisposition towards anxiety. The current research aimed to explore…

The use of emotions in narratives in Williams syndrome.

PubMed

Van Herwegen, Jo; Aznar, Ana; Tenenbaum, Harriet

2014-01-01

Although individuals with Williams syndrome are very sociable, they tend to have limited contact and friendships with peers. In typically developing children the use of positive emotions (e.g., happy) has been argued to be related to peer relationships and popularity. The current study investigated the use and development of emotion words in Williams syndrome using cross-sectional developmental trajectories and examined children's use of different types of emotion words. Nineteen children with Williams syndrome (WS) and 20 typically developing (TD) children matched for chronological age told a story from a wordless picture book. Participants with WS produced a similar number of emotion words compared to the control group and the use of emotion words did not change when plotted against chronological age or vocabulary abilities in either group. However, participants with WS produced more emotion words about sadness. Links between emotion production and friendships as well as future studies are discussed. After reading this article, readers will be able to: explain the development of positive and negative emotions in Williams syndrome and recognize that emotion production is atypical in this population. Copyright © 2014 Elsevier Inc. All rights reserved.

Diabetes mellitus and optic atrophy: study of the Wolfram syndrome

PubMed

Rivas-Gómez, Bernardette; Reza-Albarrán, Alfredo Adolfo

2017-01-01

Wolfram syndrome (WS), also known by the acronym DIDMOAD, is a rare and progresive hereditary disease of autosomal recessive inheritance which minimum ascertainment diagnostic criteria are the occurrence together of diabetes mellitus and optic atrophy before 15 years of age. To describe the clinical, biochemical and molecular profile of WS in a tertiary care hospital in Mexico. We reviewed patients records who fulfill the minimum ascertainment diagnostic criteria of WS presenting between January 1987 and May 2015 in a tertiary care hospital in Mexico. Five patients fulfill the inclusion criteria (three male and two female). Diabetes mellitus was the first manifestation of the syndrome in all of them, with a mean age at diagnosis of 5.8 ± 2.71 years, while the WS diagnosis was established at a mean age of 15.8 ± 8.37 years. All the patients had optic atrophy and two of them presented with the complete DIDMOAD spectrum. We found new associations with autoimmune hepatitis and testicular cancer. This study shows the variability of clinical presentation of WS, as well as two new associations. Copyright: © 2017 SecretarÍa de Salud

Extending WS-Agreement with Multi-round Negotiation Capability

NASA Astrophysics Data System (ADS)

Rumpl, Angela; Wäldrich, Oliver; Ziegler, Wolfgang

The WS-Agreement specification of the Open Grid Forum defines a language and a protocol for advertising the capabilities of service providers and creating agreements based on templates, and for monitoring agreement compliance at runtime. While the specification, which currently is in the process of transition from a proposed recommendation of the Open Grid Forum to a full recommendation, has been widely used after the initial publication in May 2007, it became obvious that the missing possibility to negotiate an agreement rather than just accepting an offer is limiting or inhibiting the use of WS-Agreement for a number of use-cases. Therefore, the Grid Resource Allocation Agreement Working Group of the Open Grid Forum started in 2008 to prepare an extension of WS-Agreement that adds negotiation capabilities without changing the current specification in a way, which leads to an incompatible new version of WS-Agreement. In this paper we present the results of this process with an updated version of the specification in mind and the first implementation in the European project SmartLM.

The social phenotype of Williams syndrome.

PubMed

Järvinen, Anna; Korenberg, Julie R; Bellugi, Ursula

2013-06-01

Williams syndrome (WS) offers an exciting model for social neuroscience because its genetic basis is well-defined, and the unique phenotype reflects dimensions of prosocial behaviors. WS is associated with a strong drive to approach strangers, a gregarious personality, heightened social engagement yet difficult peer interactions, high nonsocial anxiety, unusual bias toward positive affect, and diminished sensitivity to fear. New neurobiological evidence points toward alterations in structure, function, and connectivity of the social brain (amygdala, fusiform face area, orbital-frontal regions). Recent genetic studies implicate gene networks in the WS region with the dysregulation of prosocial neuropeptides. The study of WS has implications for understanding human social development, and may provide insight for translating genetic and neuroendocrine evidence into treatments for disorders of social behavior. Copyright © 2013 Elsevier Ltd. All rights reserved.

Microsteganography on WS2 Monolayers Tailored by Direct Laser Painting.

PubMed

Venkatakrishnan, Ashwin; Chua, Hou; Tan, Pinxi; Hu, Zhenliang; Liu, Hongwei; Liu, Yanpeng; Carvalho, Alexandra; Lu, Junpeng; Sow, Chorng Haur

2017-01-24

We present scanning focused laser beam as a multipurpose tool to engineer the physical and chemical properties of WS 2 microflakes. For monolayers, the laser modification integrates oxygen into the WS 2 microflake, resulting in ∼9 times enhancement in the intensity of the fluorescence emission. This modification does not cause any morphology change, allowing "micro-encryption" of information that is only observable as fluorescence under excitation. The same focused laser also facilitates on demand thinning down of WS 2 multilayers into monolayers, turning them into fluorescence active components. With a scanning focused laser beam, micropatterns are readily created on WS 2 multilayers through selective thinning of specific regions on the flake.

Recent Trends in WRN Gene Mutation Patterns in Individuals with Werner Syndrome.

PubMed

Yamaga, Masaya; Takemoto, Minoru; Takada-Watanabe, Aki; Koizumi, Naoko; Kitamoto, Takumi; Sakamoto, Kenichi; Ishikawa, Takahiro; Koshizaka, Masaya; Maezawa, Yoshiro; Yokote, Koutaro

2017-08-01

To determine recent trends in mutation patterns in the WRN gene, which cause Werner syndrome (WS), a rare, inheritable progeroid syndrome in Japan. Retrospective cohort. Longitudinal survey of WS and literature search for case reports. Individuals whose genetic testing their facilities had requested between 2009 and October 2016 (N = 67). A nationwide epidemiological study was conducted from 2009 to 2011 to improve understanding of the pathology of WS and develop therapeutic guidelines. Since 2009, Chiba University Hospital consecutively evaluated the WRN gene in 67 individuals throughout Japan who had requested genetic testing. A literature search was also conducted for case reports on Japanese WS reported since 1997. A definitive diagnosis of WS was confirmed genetically in 50 of 67 participants. Through the literature search, 16 individuals diagnosed genetically with WS were identified. Of these 66 individuals with WS, 42 were homozygous for a WRN mutation, and 21 were compound heterozygotes. One novel mutant allele was identified in an individual with the compound heterozygous genotype. The proportion of compound heterozygotes (31.8%) was significantly greater than reported previously (14.2%), indicating that the incidence of consanguineous marriage of parents has decreased. The increased frequency of individuals with WS with the compound heterozygous genotype is a recent trend in Japan. A long-term follow-up study on WRN homozygotes and compound heterozygotes will allow the relationship between WRN genotype and clinical severity of WS to be evaluated in the future. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Adaptive Behavior and Problem Behavior in Young Children with Williams Syndrome

ERIC Educational Resources Information Center

Hahn, Laura J.; Fidler, Deborah J.; Hepburn, Susan L.

2014-01-01

The present study compares the adaptive behavior profile of 18 young children with Williams syndrome (WS) and a developmentally matched group of 19 children with developmental disabilities and examines the relationship between adaptive behavior and problem behaviors in WS. Parents completed the Vineland Adaptive Behavioral Scales--Interview…

Multi-walled carbon/IF-WS2 nanoparticles with improved thermal properties.

PubMed

Xu, Fang; Almeida, Trevor P; Chang, Hong; Xia, Yongde; Wears, M Lesley; Zhu, Yanqiu

2013-11-07

A unique new class of core-shell structured composite nanoparticles, C-coated inorganic fullerene-like WS2 (IF-WS2) hollow nanoparticles, has been created for the first time in large quantities, by a continuous chemical vapour deposition method using a rotary furnace. Transmission electron microscopy and Raman characterisations of the resulting samples reveal that the composite nanoparticles exhibited a uniform shell of carbon coating, ranging from 2-5 nm on the IF-WS2 core, with little or no agglomeration. Importantly, thermogravimetric analysis and differential scanning calorimetry analysis confirm that their thermal stability against oxidation in air has been improved by about 70 °C, compared to the pristine IF-WS2, making these new C-coated IF-WS2 nanoparticles more attractive for critical engineering applications.

[Wolfram syndrome: from definition to molecular bases].

PubMed

Ribeiro, Maria Regina F; Crispim, Felipe; Vendramini, Márcio F; Moisés, Regina S

2006-10-01

Wolfram syndrome (WS) is an autosomal recessive progressive neurodegenerative disorder characterized by diabetes mellitus and optic atrophy. Diabetes insipidus and sensorineural deafness are also noted frequently, explaining the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) by which the syndrome is also referred. Additional manifestations such as atonic bladder, ataxia, nystagmus and predisposition for psychiatric illness may be present. The Wolfram syndrome gene, WFS1, was mapped to chromosome 4p16.1 by positional cloning. It encodes an 890-amino-acid polypeptide named wolframin. Although the wolframin function is still not completely known, its localization to the endoplasmic reticulum suggests it can play a role in calcium homeostasis, membrane trafficking and protein processing. Knowing the cellular function of wolframin is necessary for understanding the pathophysiology of Wolfram syndrome. This knowledge may lead to development of therapies to prevent or reduce the outcomes of WS.

Neuron density is decreased in the prefrontal cortex in Williams syndrome.

PubMed

Lew, Caroline Horton; Brown, Chelsea; Bellugi, Ursula; Semendeferi, Katerina

2017-01-01

Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with a hemideletion in chromosome 7, which manifests a distinct behavioral phenotype characterized by a hyperaffiliative social drive, in striking contrast to the social avoidance behaviors that are common in Autism Spectrum Disorder (ASD). MRI studies have observed structural and functional abnormalities in WS cortex, including the prefrontal cortex (PFC), a region implicated in social cognition. This study utilizes the Bellugi Williams Syndrome Brain Collection, a unique resource that comprises the largest WS postmortem brain collection in existence, and is the first to quantitatively examine WS PFC cytoarchitecture. We measured neuron density in layers II/III and V/VI of five cortical areas: PFC areas BA 10 and BA 11, primary motor BA 4, primary somatosensory BA 3, and visual area BA 18 in six matched pairs of WS and typically developing (TD) controls. Neuron density in PFC was lower in WS relative to TD, with layers V/VI demonstrating the largest decrease in density, reaching statistical significance in BA 10. In contrast, BA 3 and BA 18 demonstrated a higher density in WS compared to TD, although this difference was not statistically significant. Neuron density in BA 4 was similar in WS and TD. While other cortical areas were altered in WS, prefrontal areas appeared to be most affected. Neuron density is also altered in the PFC of individuals with ASD. Together these findings suggest that the PFC is targeted in neurodevelopmental disorders associated with sociobehavioral alterations. Autism Res 2017, 10: 99-112. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Beat Perception and Sociability: Evidence from Williams Syndrome

PubMed Central

Lense, Miriam D.; Dykens, Elisabeth M.

2016-01-01

Beat perception in music has been proposed to be a human universal that may have its origins in adaptive processes involving temporal entrainment such as social communication and interaction. We examined beat perception skills in individuals with Williams syndrome (WS), a genetic, neurodevelopmental disorder. Musical interest and hypersociability are two prominent aspects of the WS phenotype although actual musical and social skills are variable. On a group level, beat and meter perception skills were poorer in WS than in age-matched peers though there was significant individual variability. Cognitive ability, sound processing style, and musical training predicted beat and meter perception performance in WS. Moreover, we found significant relationships between beat and meter perception and adaptive communication and socialization skills in WS. Results have implications for understanding the role of predictive timing in both music and social interactions in the general population, and suggest music as a promising avenue for addressing social communication difficulties in WS. PMID:27378982

Parent and Self-Report Ratings on the Perceived Levels of Social Vulnerability of Adults with Williams Syndrome

ERIC Educational Resources Information Center

Lough, Emma; Fisher, Marisa H.

2016-01-01

The current study took a multi-informant approach to compare parent to self-report ratings of social vulnerability of adults with Williams syndrome (WS). Participants included 102 pairs of adults with WS and their parents. Parents completed the "Social Vulnerability Questionnaire" and adults with WS completed an adapted version of the…

A method for determining haploid and triploid genotypes and their association with vascular phenotypes in Williams syndrome and 7q11.23 duplication syndrome.

PubMed

Gregory, Michael D; Kolachana, Bhaskar; Yao, Yin; Nash, Tiffany; Dickinson, Dwight; Eisenberg, Daniel P; Mervis, Carolyn B; Berman, Karen F

2018-04-04

Williams syndrome ([WS], 7q11.23 hemideletion) and 7q11.23 duplication syndrome (Dup7) show contrasting syndromic symptoms. However, within each group there is considerable interindividual variability in the degree to which these phenotypes are expressed. Though software exists to identify areas of copy number variation (CNV) from commonly-available SNP-chip data, this software does not provide non-diploid genotypes in CNV regions. Here, we describe a method for identifying haploid and triploid genotypes in CNV regions, and then, as a proof-of-concept for applying this information to explain clinical variability, we test for genotype-phenotype associations. Blood samples for 25 individuals with WS and 13 individuals with Dup7 were genotyped with Illumina-HumanOmni5M SNP-chips. PennCNV and in-house code were used to make genotype calls for each SNP in the 7q11.23 locus. We tested for association between the presence of aortic arteriopathy and genotypes of the remaining (haploid in WS) or duplicated (triploid in Dup7) alleles. Haploid calls in the 7q11.23 region were made for 99.0% of SNPs in the WS group, and triploid calls for 98.8% of SNPs in those with Dup7. The G allele of SNP rs2528795 in the ELN gene was associated with aortic stenosis in WS participants (p < 0.0049) while the A allele of the same SNP was associated with aortic dilation in Dup7. Commonly available SNP-chip information can be used to make haploid and triploid calls in individuals with CNVs and then to relate variability in specific genes to variability in syndromic phenotypes, as demonstrated here using aortic arteriopathy. This work sets the stage for similar genotype-phenotype analyses in CNVs where phenotypes may be more complex and/or where there is less information about genetic mechanisms.

Children with Praderwilli Syndrome Vs. Williams Syndrome: Indirect Effects on Parents during a Jigsaw Puzzle Task

ERIC Educational Resources Information Center

Ly, T. M.; Hodapp, R. M.

2005-01-01

Background: Genetic disorders predispose individuals to exhibit characteristic behaviours, which in turn elicit particular behaviours from others. In response to the strength of Prader?Willi syndrome (PWS) and weakness of Williams syndrome (WS) in visual-spatial tasks such as jigsaw puzzles, parents' behaviours can be affected by their child's…

WS-BP: An efficient wolf search based back-propagation algorithm

NASA Astrophysics Data System (ADS)

Nawi, Nazri Mohd; Rehman, M. Z.; Khan, Abdullah

2015-05-01

Wolf Search (WS) is a heuristic based optimization algorithm. Inspired by the preying and survival capabilities of the wolves, this algorithm is highly capable to search large spaces in the candidate solutions. This paper investigates the use of WS algorithm in combination with back-propagation neural network (BPNN) algorithm to overcome the local minima problem and to improve convergence in gradient descent. The performance of the proposed Wolf Search based Back-Propagation (WS-BP) algorithm is compared with Artificial Bee Colony Back-Propagation (ABC-BP), Bat Based Back-Propagation (Bat-BP), and conventional BPNN algorithms. Specifically, OR and XOR datasets are used for training the network. The simulation results show that the WS-BP algorithm effectively avoids the local minima and converge to global minima.

Personal Space Regulation in Williams Syndrome: The Effect of Familiarity

ERIC Educational Resources Information Center

Lough, Emma; Flynn, Emma; Riby, Deborah M.

2016-01-01

Personal space refers to a protective barrier that we strive to maintain around our body. We examined personal space regulation in young people with Williams syndrome (WS) and their typically developing, chronological age-matched peers using a parent report questionnaire and a stop-distance paradigm. Individuals with WS were reported by their…

Functional basic reading skills in Williams syndrome.

PubMed

Brawn, Gabrielle; Kohnen, Saskia; Tassabehji, May; Porter, Melanie

2018-03-30

This study investigated whether individuals with Williams syndrome (WS) can attain a functional level of basic reading skills. The Study also investigated broader cognitive factors associated with reading ability in individuals with WS. Thirty individuals with WS participated in this study (mean chronological age 21 years and mean mental age 7 years 7 months). The results supported our hypotheses that: firstly, reading abilities would be heterogeneous in WS; secondly, at least some WS individuals are capable of achieving a functional basic reading level; and thirdly, on average, WS individuals would find reading of nonwords more difficult than reading of regular and irregular words. Moreover, higher reading ability was found to be associated with increased outcomes in adaptive functioning, in particular, Written and Expressive Communication skills and Community Living skills, highlighting the potential benefits of developing reading abilities in WS. Although Intelligence Quotient (IQ) was related to overall basic reading ability generally, it was not found to be a determining factor in reading subtypes. Several cognitive skills known to be related to reading ability in typically developing individuals were found to be associated with reading performance and reading subtypes. Implications for appropriate reading instruction are discussed.

A human neurodevelopmental model for Williams syndrome

PubMed Central

Chailangkarn, Thanathom; Trujillo, Cleber A.; Freitas, Beatriz C.; Hrvoj-Mihic, Branka; Herai, Roberto H.; Yu, Diana X.; Brown, Timothy T.; Marchetto, Maria C. N.; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M.; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M. Colin; Hanson, Kari L.; Romero, Sarah; Jacobs, Bob; Dale, Anders M.; Dai, Li; Korenberg, Julie R.; Gage, Fred H.; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R.

2016-01-01

Summary Williams syndrome (WS) is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with WS lack precisely the same set of genes, with breakpoints in chromosome band 7q11.231–5. The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioral pathologies in humans, remains largely unexplored. Here, we investigate neural progenitor cells (NPCs) and cortical neurons derived from WS and typically developing (TD) induced pluripotent stem cells (iPSCs). WS NPCs have an increased doubling time and apoptosis compared to TD NPCs. Using an atypical WS subject6, 7, we narrowed this cellular phenotype to a single gene candidate, FZD9. At the neuronal stage, WS-derived layers V/VI cortical neurons were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in WS neurons were validated after Golgi staining of postmortem layers V/VI cortical neurons. This human iPSC model8 fills in the current knowledge gap in WS cellular biology and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain. PMID:27509850

Williams syndrome-specific neuroanatomical profile and its associations with behavioral features.

PubMed

Fan, Chun Chieh; Brown, Timothy T; Bartsch, Hauke; Kuperman, Joshua M; Hagler, Donald J; Schork, Andrew; Searcy, Yvonne; Bellugi, Ursula; Halgren, Eric; Dale, Anders M

2017-01-01

Williams Syndrome (WS) is a rare genetic disorder with unique behavioral features. Yet the rareness of WS has limited the number and type of studies that can be conducted in which inferences are made about how neuroanatomical abnormalities mediate behaviors. In this study, we extracted a WS-specific neuroanatomical profile from structural magnetic resonance imaging (MRI) measurements and tested its association with behavioral features of WS. Using a WS adult cohort (22 WS, 16 healthy controls), we modeled a sparse representation of a WS-specific neuroanatomical profile. The predictive performances are robust within the training cohort (10-fold cross-validation, AUC = 1.0) and accurately identify all WS individuals in an independent child WS cohort (seven WS, 59 children with diverse developmental status, AUC = 1.0). The WS-specific neuroanatomical profile includes measurements in the orbitofrontal cortex, superior parietal cortex, Sylvian fissures, and basal ganglia, and variability within these areas related to the underlying size of hemizygous deletion in patients with partial deletions. The profile intensity mediated the overall cognitive impairment as well as personality features related to hypersociability. Our results imply that the unique behaviors in WS were mediated through the constellation of abnormalities in cortical-subcortical circuitry consistent in child WS and adult WS. The robustness of the derived WS-specific neuroanatomical profile also demonstrates the potential utility of our approach in both clinical and research applications.

Eye Development Genes and Known Syndromes

PubMed Central

Slavotinek, Anne M.

2011-01-01

Anophthalmia and microphthalmia (A/M) are significant eye defects because they can have profound effects on visual acuity. A/M is associated with non-ocular abnormalities in an estimated 33–95% of cases and around 25% of patients have an underlying genetic syndrome that is diagnosable. Syndrome recognition is important for targeted molecular genetic testing, prognosis and for counseling regarding recurrence risks. This review provides clinical and molecular information for several of the commonest syndromes associated with A/M: Anophthalmia-Esophageal-Genital syndrome, caused by SOX2 mutations, Anophthalmia and pituitary abnormalities caused by OTX2 mutations, Matthew-Wood syndrome caused by STRA6 mutations, Oculocardiafaciodental syndrome and Lenz microphthalmia caused by BCOR mutations, Microphthalmia Linear Skin pigmentation syndrome caused by HCCS mutations, Anophthalmia, pituitary abnormalities, polysyndactyly caused by BMP4 mutations and Waardenburg anophthalmia caused by mutations in SMOC1. In addition, we briefly discuss the ocular and extraocular phenotypes associated with several other important eye developmental genes, including GDF6, VSX2, RAX, SHH, SIX6 and PAX6. PMID:22005280

Attribution of negative intention in Williams syndrome.

PubMed

Godbee, Kali; Porter, Melanie A

2013-05-01

People with Williams syndrome (WS) are said to have sociable and extremely trusting personalities, approaching strangers without hesitation. This study investigated whether people with WS are less likely than controls to attribute negative intent to others when interpreting a series of ambiguous pictures. This may, at least partially, explain their hypersociability toward strangers. Twenty-seven individuals with WS and 54 typically developing controls (27 matched to WS participants on sex and chronological age and 27 matched on sex and mental age) viewed 10 ambiguous pictures, where one person in the picture may be seen as having a negative objective. Participants were asked to describe what was happening in the picture. Responses were scored for negative intention attribution (NIA). NIA was reduced in WS individuals relative to typically developing controls of the same chronological age, but was similar to typically developing controls of the same mental age. Findings are discussed in relation to possible underlying neurological and cognitive mechanisms and practical implications for understanding and teaching stranger danger to people with WS. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Williams Syndrome: A Critical Review of the Cognitive, Behavioral, and Neuroanatomical Phenotype

ERIC Educational Resources Information Center

Martens, Marilee A.; Wilson, Sarah J.; Reutens, David C.

2008-01-01

This review critically examines the research findings which characterize the cognitive, behavioral, and neuroanatomical features of Williams syndrome (WS). This article analyzes 178 published studies in the WS literature covering the following areas: 1) General intelligence, 2) Language skills, 3) Visuospatial and face processing skills, 4)…

IF-WS{sub 2} nanoparticles size design and synthesis via chemical reduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghoreishi, S.M., E-mail: ghoreshi@cc.iut.ac.ir; Meshkat, S.S.; Dadkhah, A.A.

2010-05-15

An innovative synthesis of inorganic fullerene-like disulfide tungsten (IF-WS{sub 2}) nanoparticles was developed using a chemical reduction reaction in a horizontal quartz reactor. In this process, first tungsten trisulfide (WS{sub 3}) was formed via a chemical reaction of tetra thiotungstate ammonium ((NH{sub 4}){sub 2}WS{sub 4}), polyethylene glycol (PEG), and hydrochloric acid (HCl) at ambient temperature and pressure. Subsequently, WS{sub 3} was reacted with hydrogen (H{sub 2}) at high temperature (1173-1373 K) in a quartz tube. The produced WS{sub 2} nanoparticles were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDAX), and transmission electron microscopy (TEM). Themore » characterization results indicated that the high-purity (100%) IF-WS{sub 2} nanoparticles were produced. Moreover, addition of surfactant (PEG) and higher operating temperature (1173-1373 K) decreased the particles agglomeration, and consequently led to the reduction of average diameter of WS{sub 2} particles in the range of 50-78 nm. The developed method is simple, environmentally compatible, and cost-effective in contrast to the conventional techniques.« less

Idiom Comprehension in French-Speaking Children and Adolescents with Williams' Syndrome

ERIC Educational Resources Information Center

Lacroix, Agnes; Aguert, Marc; Dardier, Virginie; Stojanovik, Vesna; Laval, Virginie

2010-01-01

This study looks at idiom comprehension by French-speaking people with Williams' syndrome (WS) and metapragmatic knowledge is examined. Idiomatic expressions are a nonliteral form of language where there is a considerable difference between what is said (literal interpretation) and what is meant (idiomatic interpretation). WS is characterized by a…

Photoluminescence inhomogeneity and excitons in CVD-grown monolayer WS2

NASA Astrophysics Data System (ADS)

Ren, Dan-Dan; Qin, Jing-Kai; Li, Yang; Miao, Peng; Sun, Zhao-Yuan; Xu, Ping; Zhen, Liang; Xu, Cheng-Yan

2018-06-01

Transition metal dichalcogenides two-dimensional materials are of great importance for future electronic and optoelectronic applications. In this work, triangular WS2 monolayers with size up to 130 μm were prepared via chemical vapor deposition method. WS2 monolayers presented uniform Raman intensity, while quenched photoluminescence (PL) was observed in the center. The PL quenching in the central part of WS2 monolayer flakes was attributed to the gradually increasing sulfur vacancies toward the center. The proportion of negative trion (X-) in PL spectrum increases with increasing sulfur vacancies in WS2. The enhanced binding energy of X- suggests higher Fermi level and n-doping level with larger sulfur vacancy concentration. Our findings may be beneficial to the development of integrated devices, and also explore the defect-induced optical and electrical properties for nanophotonics.

Sleep phenotypes in infants and toddlers with neurogenetic syndromes.

PubMed

Abel, Emily A; Tonnsen, Bridgette L

2017-10-01

Although sleep problems are well characterized in preschool- and school-age children with neurogenetic syndromes, little is known regarding the early emergence of these problems in infancy and toddlerhood. To inform syndrome-specific profiles and targets for intervention, we compared parent-reported sleep problems in infants and toddlers with Angelman syndrome (AS), Williams syndrome (WS), and Prader-Willi syndrome (PWS) with patterns observed among same-aged typically developing (TD) controls. Mothers of 80 children (18 AS, 19 WS, 19 PWS, and 24 TD) completed the Brief Infant Sleep Questionnaire. Primary dependent variables included (1) sleep onset latency, (2) total sleep duration, (3) daytime and nighttime sleep duration, and (4) sleep problem severity, as measured by both maternal impression and National Sleep Foundation guidelines. Sleep problems are relatively common in children with neurogenetic syndromes, with 41% of mothers reporting problematic sleep and 29% of children exhibiting abnormal sleep durations as per national guidelines. Across genetic subgroups, problems are most severe in children with AS and WS, particularly in relation to nighttime sleep duration. Although atypical sleep is characteristically reported in each syndrome later in development, infants and toddlers with PWS exhibited largely typical patterns, potentially indicating delayed onset of sleep problems in concordance with other medical features of PWS. Our findings suggest that sleep problems in neurogenetic syndromes emerge as early as infancy and toddlerhood, with variable profiles across genetic subgroups. This work underscores the importance of early sleep screenings as part of routine medical care of neurosyndromic populations and the need for targeted, syndrome-sensitive treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Longitudinal Trajectories of Intellectual and Adaptive Functioning in Adolescents and Adults with Williams Syndrome

ERIC Educational Resources Information Center

Fisher, M. H.; Lense, M. D.; Dykens, E. M.

2016-01-01

Background: Williams syndrome (WS) is associated with a distinct cognitive-behavioural phenotype including mild to moderate intellectual disability, visual-spatial deficits, hypersociability, inattention and anxiety. Researchers typically characterise samples of individuals with WS by their intellectual functioning and adaptive behaviour. Because…

Children with Prader-Willi syndrome vs. Williams syndrome: indirect effects on parents during a jigsaw puzzle task.

PubMed

Ly, T M; Hodapp, R M

2005-12-01

Genetic disorders predispose individuals to exhibit characteristic behaviours, which in turn elicit particular behaviours from others. In response to the strength of Prader-Willi syndrome (PWS) and weakness of Williams syndrome (WS) in visual-spatial tasks such as jigsaw puzzles, parents' behaviours can be affected by their child's level of puzzle ability or syndrome diagnosis. Children were asked to complete two jigsaw puzzles (one with the experimenter and the other with the parent) for 5 min each. Frequencies of parental helping and reinforcement behaviours, along with ratings of parental directiveness, were examined as parents interacted with their children on a jigsaw puzzle task. Within each aetiological group, correlates of parental behaviours with child characteristics were also examined. Compared to parents of children with PWS, parents of children with WS engaged in a more directive style of interaction, and provided more help and reinforcement. Relative to parents of children with higher puzzle abilities (from both aetiologies), parents of children with lower abilities also showed the same pattern. Both the child's aetiology and puzzle abilities were important in predicting parents' directiveness and helping and reinforcement behaviours. Within the PWS group, parents' behaviours correlated negatively with the child's puzzle abilities and general cognitive functioning; no such relations occurred in the WS group. Parents' behaviours were affected by both the child's diagnosis and actual puzzle abilities, suggesting important implications for understanding and intervening with parents and children with different genetic syndromes.

Peri-procedural risk stratification and management of patients with Williams syndrome.

PubMed

Collins Ii, R Thomas; Collins, Margaret G; Schmitz, Michael L; Hamrick, Justin T

2017-03-01

Williams syndrome (WS) is a congenital, multisystem disorder affecting the cardiovascular, connective tissue, and central nervous systems in 1 in 10 000 live births. Cardiovascular involvement is the most common cause of morbidity and mortality in patients with WS, and noninvasive and invasive procedures are common. Sudden cardiovascular collapse in patients with WS is a well-known phenomenon, especially in the peri-procedural period. Detailed guidelines for peri-procedural management of patients with WS are limited. The goal of this review is to provide thoughtful, safe and effective management strategies for the peri-procedural care of patients with WS with careful consideration of hemodynamic impacts of anesthetic strategies. In addition, an expanded risk stratification system for anesthetic administration is provided. © 2017 Wiley Periodicals, Inc.

Capacity to improve fine motor skills in Williams syndrome.

PubMed

Berencsi, A; Gombos, F; Kovács, I

2016-10-01

Individuals with Williams syndrome (WS) are known to have difficulties in carrying out fine motor movements; however, a detailed behavioural profile of WS in this domain is still missing. It is also unknown how great the capacity to improve these skills with focused and extensive practice is. We studied initial performance and learning capacity in a sequential finger tapping (FT) task in WS and in typical development. Improvement in the FT task has been shown to be sleep dependent. WS subjects participating in the current study have also participated in earlier polysomnography studies, although not directly related to learning. WS participants presented with great individual variability. In addition to generally poor initial performance, learning capacity was also greatly limited in WS. We found indications that reduced sleep efficiency might contribute to this limitation. Estimating motor learning capacity and the depth of sleep disorder in a larger sample of WS individuals might reveal important relationships between sleep and learning, and contribute to efficient intervention methods improving skill acquisition in WS. © 2016 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Contrast-Marking Prosodic Emphasis in Williams Syndrome: Results of Detailed Phonetic Analysis

ERIC Educational Resources Information Center

Ito, Kiwako; Martens, Marilee A.

2017-01-01

Background: Past reports on the speech production of individuals with Williams syndrome (WS) suggest that their prosody is anomalous and may lead to challenges in spoken communication. While existing prosodic assessments confirm that individuals with WS fail to use prosodic emphasis to express contrast, those reports typically lack detailed…

Evaluation of a Stranger Safety Training Programme for Adults with Williams Syndrome

ERIC Educational Resources Information Center

Fisher, M. H.

2014-01-01

Background: Individuals with Williams syndrome (WS) are reported to display increased sociability towards strangers, leading to increased social vulnerability. No research has examined real life interactions of adults with WS towards strangers and no interventions have been implemented to teach stranger safety skills to this population. Method:…

Elicited Production of Relative Clauses in Children with Williams Syndrome

ERIC Educational Resources Information Center

Zukowski, Andrea

2009-01-01

Relative clauses have been implicated alternately as a strength and a weakness in the language of people with Williams Syndrome (WS). To clarify the facts, an elicited production test was administered to 10 people with WS (age 10-16 years), 10 typically developing children (age 4-7 years), and 12 typically developing adults. Nearly every WS…

Prosodic Abilities of Spanish-Speaking Adolescents and Adults with Williams Syndrome

ERIC Educational Resources Information Center

Martinez-Castilla, Pastora; Sotillo, Maria; Campos, Ruth

2011-01-01

In spite of the relevant role of prosody in communication, and in contrast with other linguistic components, there is paucity of research in this field for Williams syndrome (WS). Therefore, this study performed a systematic assessment of prosodic abilities in WS. The Spanish version of the Profiling Elements of Prosody in Speech-Communication…

Syndromes, disorders and maternal risk factors associated with neural tube defects (I).

PubMed

Chen, Chih-Ping

2008-03-01

Fetuses with neural tube defects (NTDs) may be associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as acrocallosal syndrome, autosomal dominant brachydactyly-clinodactyly syndrome, Manouvrier syndrome, short rib-polydactyly syndrome, Disorganization ( Ds )-like human malformations, isolated hemihyperplasia, X-linked NTDs, meroanencephaly, schisis association, diprosopus, fetal valproate syndrome, DiGeorge syndrome/velocardiofacial syndrome, Waardenburg syndrome, folic acid antagonists, diabetes mellitus, and obesity. NTDs associated with syndromes, disorders, and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls.

PubMed

Vega, Jennifer N; Hohman, Timothy J; Pryweller, Jennifer R; Dykens, Elisabeth M; Thornton-Wells, Tricia A

2015-10-01

The emergence of resting-state functional connectivity (rsFC) analysis, which examines temporal correlations of low-frequency (<0.1 Hz) blood oxygen level-dependent signal fluctuations between brain regions, has dramatically improved our understanding of the functional architecture of the typically developing (TD) human brain. This study examined rsFC in Down syndrome (DS) compared with another neurodevelopmental disorder, Williams syndrome (WS), and TD. Ten subjects with DS, 18 subjects with WS, and 40 subjects with TD each participated in a 3-Tesla MRI scan. We tested for group differences (DS vs. TD, DS vs. WS, and WS vs. TD) in between- and within-network rsFC connectivity for seven functional networks. For the DS group, we also examined associations between rsFC and other cognitive and genetic risk factors. In DS compared with TD, we observed higher levels of between-network connectivity in 6 out 21 network pairs but no differences in within-network connectivity. Participants with WS showed lower levels of within-network connectivity and no significant differences in between-network connectivity relative to DS. Finally, our comparison between WS and TD controls revealed lower within-network connectivity in multiple networks and higher between-network connectivity in one network pair relative to TD controls. While preliminary due to modest sample sizes, our findings suggest a global difference in between-network connectivity in individuals with neurodevelopmental disorders compared with controls and that such a difference is exacerbated across many brain regions in DS. However, this alteration in DS does not appear to extend to within-network connections, and therefore, the altered between-network connectivity must be interpreted within the framework of an intact intra-network pattern of activity. In contrast, WS shows markedly lower levels of within-network connectivity in the default mode network and somatomotor network relative to controls. These findings

Exciton broadening in WS 2 /graphene heterostructures

DOE PAGES

Hill, Heather M.; Rigosi, Albert F.; Raja, Archana; ...

2017-11-01

Here, we have used optical spectroscopy to observe spectral broadening of WS 2 exciton reflectance peaks in heterostructures of monolayer WS 2 capped with mono- to few-layer graphene. The broadening is found to be similar for the A and B excitons and on the order of 5–10 meV. No strong dependence on the number of graphene layers was observed within experimental uncertainty. The broadening can be attributed to charge- and energy-transfer processes between the two materials, providing an observed lower bound for the corresponding time scales of 65 fs.

Perceptual learning in Williams syndrome: looking beyond averages.

PubMed

Gervan, Patricia; Gombos, Ferenc; Kovacs, Ilona

2012-01-01

Williams Syndrome is a genetically determined neurodevelopmental disorder characterized by an uneven cognitive profile and surprisingly large neurobehavioral differences among individuals. Previous studies have already shown different forms of memory deficiencies and learning difficulties in WS. Here we studied the capacity of WS subjects to improve their performance in a basic visual task. We employed a contour integration paradigm that addresses occipital visual function, and analyzed the initial (i.e. baseline) and after-learning performance of WS individuals. Instead of pooling the very inhomogeneous results of WS subjects together, we evaluated individual performance by expressing it in terms of the deviation from the average performance of the group of typically developing subjects of similar age. This approach helped us to reveal information about the possible origins of poor performance of WS subjects in contour integration. Although the majority of WS individuals showed both reduced baseline and reduced learning performance, individual analysis also revealed a dissociation between baseline and learning capacity in several WS subjects. In spite of impaired initial contour integration performance, some WS individuals presented learning capacity comparable to learning in the typically developing population, and vice versa, poor learning was also observed in subjects with high initial performance levels. These data indicate a dissociation between factors determining initial performance and perceptual learning.

Looking at Movies and Cartoons: Eye-Tracking Evidence from Williams Syndrome and Autism

ERIC Educational Resources Information Center

Riby, D.; Hancock, P. J. B.

2009-01-01

Background: Autism and Williams syndrome (WS) are neuro-developmental disorders associated with distinct social phenotypes. While individuals with autism show a lack of interest in socially important cues, individuals with WS often show increased interest in socially relevant information. Methods: The current eye-tracking study explores how…

Cortisol Reactivity and Performance Abilities in Social Situations in Adults with Williams Syndrome

ERIC Educational Resources Information Center

Lense, Miriam D.; Dykens, Elisabeth M.

2013-01-01

Williams syndrome (WS) is a neurodevelopmental disorder associated with hypersociability and anxiety. However, little is known about how these salient aspects of the phenotype are related or their underlying physiology. We examined cortisol reactivity in WS because cortisol is responsive to psychosocial stress. Compared to typically developing…

Versatile soliton emission from a WS2 mode-locked fiber laser

NASA Astrophysics Data System (ADS)

Guo, Bo; Li, Shi; Fan, Ya-xian; Wang, Pengfei

2018-01-01

Recently, few-layer tungsten disulfide (WS2), as a shining 2D material, has been discovered to possess both the saturable absorption ability and large nonlinear refractive index. Here, we demonstrate versatile soliton pulses in a passively mode-locked fiber laser with a WS2-deposited microfiber. The few-layer WS2 is prepared by the liquid-phase exfoliation method and transferred onto a microfiber by the optical deposition method. Study found, the WS2-deposited microfiber can operate simultaneously as a mode-locker and a high-nonlinear device. In experiment, by further inserting the WS2 device into the fiber laser, besides the dual-wavelength soliton, noise-like soliton pulse, conventional soliton and its harmonic form are obtained by properly adjusting the pump strength and the polarization states. For the dual-wavelength soliton pulses and noise-like pulse, the maximum output power of 14.2 mW and pulse energy of 4.74 nJ is obtained, respectively. In addition, we also achieve the maximum harmonic number (135) of conventional soliton, corresponding to a repetition rate of ∼ 497 . 5 MHz. Our study shows clearly that WS2-deposited microfiber can be as a high-nonlinear photonic device for studying a plenty of nonlinear soliton phenomena.

The regulatory function of social referencing in preschoolers with Down syndrome or Williams syndrome

PubMed Central

2013-01-01

Background An important developmental task is to learn to recognize another person as a source of information and to utilize this information as a method of learning about the surrounding world. This socially guided form of learning, referred to as social referencing, is critical for the development of children’s understanding of other people, themselves and their surrounding world. In the present project, the regulatory function of social referencing was examined in two genetic disorders that are characterized by differing patterns of socio-cognitive development: Down syndrome (DS) and Williams syndrome (WS). Methods Participants were 20 children with DS and 20 children with WS aged 42 to 71 months, matched on chronological age and gender. Each child participated in four studies: one study in which we examined performance in a social referencing paradigm and three studies in which we considered performance on tasks designed to tap each of three component abilities (initiating eye contact, gaze following and emotional responsivity) important for success in social referencing. Results The majority of children in both groups demonstrated positive behavioral responses regarding the stimulus in the Social Referencing task when the adult communicated a joyful message but did not regulate their own behavior in accordance with the adult’s expression of fear. Between-group differences were observed in both conditions, with most differences indicating more advanced socio-communicative competence for children with DS than for children with WS even though the overall intellectual abilities and receptive language abilities of the children with WS were significantly higher than were those of the children with DS. The results of follow-up studies indicated that children with DS were more likely to initiate eye contact (unsolicited) and to follow another person’s gaze in triadic situations than were children with WS. Neither group regulated their behavior in response to

Surface functionalization of WS2 fullerene-like nanoparticles.

PubMed

Shahar, Chen; Zbaida, David; Rapoport, Lev; Cohen, Hagai; Bendikov, Tatyana; Tannous, Johny; Dassenoy, Fabrice; Tenne, Reshef

2010-03-16

WS(2) belongs to a family of layered metal dichalcogenide compounds that are known to form cylindrical (inorganic nanotubes-INT) and polyhedral nanostructures--onion or nested fullerene-like (IF) particles. The outermost layers of these IF nanoparticles can be peeled under shear stress, thus IF nanoparticles have been studied for their use as solid lubricants. However, the IF nanoparticles tend to agglomerate, presumably because of surface structural defects induced by elastic strain and curvature, a fact that has a deleterious effect on their tribological properties. In the present work, chemical modification of the IF-WS(2) surface with alkyl-silane molecules is reported. The surface-modified IF nanoparticles display improved dispersion in oil-based suspensions. The alkyl-silane coating reduces the IF-WS(2) nanoparticles' tendency to agglomerate and consequently improves the long-term tribological behavior of oil formulated with the IF additive.

Topological insulator behavior of WS{sub 2} monolayer with square-octagon ring structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Ashok, E-mail: ashok@cup.ac.in; Pandey, Ravindra; Ahluwalia, P. K.

We report electronic behavior of an allotrope of monolayer WS{sub 2} with a square octagon ring structure, refereed to as (so-WS{sub 2}) within state-of-the-art density functional theory (DFT) calculations. The WS{sub 2} monolayer shows semi-metallic characteristics with Dirac-cone like features around Γ. Unlike p-orbital’s Dirac-cone in graphene, the Dirac-cone in the so-WS{sub 2} monolayer originates from the d-electrons of the W atom in the lattice. Most interestingly, the spin-orbit interaction associated with d-electrons induce a finite band-gap that results into the metal-semiconductor transition and topological insulator-like behavior in the so-WS{sub 2} monolayer. These characteristics suggest the so-WS{sub 2} monolayer tomore » be a promising candidate for the next-generation electronic and spintronics devices.« less

Severity of Hyperacusis Predicts Individual Differences in Speech Perception in Williams Syndrome

ERIC Educational Resources Information Center

Elsabbagh, M.; Cohen, H.; Cohen, M.; Rosen, S.; Karmiloff-Smith, A.

2011-01-01

Background: Williams Syndrome (WS) is a neurodevelopmental disorder of genetic origin, characterised by relative proficiency in language in the face of serious impairment in several other domains. Individuals with WS display an unusual sensitivity to noise, known as hyperacusis. Methods: In this study, we examined the extent to which hyperacusis…

Sleep EEG Fingerprints Reveal Accelerated Thalamocortical Oscillatory Dynamics in Williams Syndrome

ERIC Educational Resources Information Center

Bodizs, Robert; Gombos, Ferenc; Kovacs, Ilona

2012-01-01

Sleep EEG alterations are emerging features of several developmental disabilities, but detailed quantitative EEG data on the sleep phenotype of patients with Williams syndrome (WS, 7q11.23 microdeletion) is still lacking. Based on laboratory (Study I) and home sleep records (Study II) here we report WS-related features of the patterns of…

Cortisol Reactivity and Performance Abilities in Social Situations in Adults with Williams Syndrome

PubMed Central

Lense, Miriam D.; Dykens, Elisabeth M.

2017-01-01

Williams syndrome (WS) is a neurodevelopmental disorder associated with hypersociability and anxiety. However, little is known about how these salient aspects of the phenotype are related or their underlying physiology. We examined cortisol reactivity in WS because cortisol is responsive to psychosocial stress. Compared to typically developing adults, adults with WS had a significant cortisol decrease in response to a challenging cognitive battery. In contrast, cortisol levels in WS stayed stable in response to a solo musical performance, and baseline cortisol levels were significantly associated with musical skill. Results indicate that people with WS respond differentially to different socially-loaded situations. Implications for salience and arousal in cognitive and social situations are discussed. PMID:24245731

Experiences of Bullying for Individuals with Williams Syndrome

ERIC Educational Resources Information Center

Fisher, Marisa H.; Lough, Emma; Griffin, Megan M.; Lane, Laurel A.

2017-01-01

Background: Individuals with intellectual disability experience high rates of bullying, but it is not known how people with specific syndromes, such as Williams syndrome (WS), experience and respond to bullying. Given their behavioral profile, including hypersociability and heightened anxiety, and their risk for experiencing other forms of…

Orientation perception in Williams Syndrome: discrimination and integration

PubMed Central

Palomares, Melanie; Landau, Barbara; Egeth, Howard

2009-01-01

Williams Syndrome (WS) is a rare neurodevelopmental disorder, which stems from a genetic deletion on chromosome 7 that causes a profound weakness in visuospatial cognition. Our current study explores how orientation perception may contribute to the visuospatial deficits in WS. In Experiment 1, we found that WS individuals and normal 3-4 year olds had similar orientation discrimination thresholds and had similar prevalence of mirror-reversal errors for diagonal targets (±45 deg). In Experiment 2, we asked whether this immaturity in orientation discrimination would also be reflected in a task requiring integration of oriented elements. We found that sensitivities of WS individuals for detecting orientation-defined contours were higher than sensitivities of normal 3-4 year olds, and were not significantly different from sensitivities of normal adults. Together, these results suggest that orientation discrimination and orientation integration have different maturational trajectories in normal development and different susceptibilities to damage in WS, which may reflect largely separate visuospatial mechanisms. PMID:19231058

The Use of Cohesive Markers in Narratives by Children with Williams Syndrome

ERIC Educational Resources Information Center

Jones, Nancy Elizabeth

2013-01-01

This study examined how children and adolescents with Williams syndrome (WS; ages 8 years, 0 months [8;0]-14;5) used referential devices (determiners and pronouns), tense, and connectives to create cohesion in oral narratives based on a storybook compared to typically developing mentally and chronologically age-matched children. WS children used…

Musicality Correlates With Sociability and Emotionality in Williams Syndrome

PubMed Central

Ng, Rowena; Lai, Philip; Levitin, Daniel J.; Bellugi, Ursula

2012-01-01

Williams Syndrome (WS) is a neurogenetic developmental disorder characterized by peaks and valleys of cognitive abilities. One peak that has been understudied is the affinity that many individuals with WS have toward music. It remains unknown whether their high levels of musical interest, skill and expressivity are related to their sociable personality or their verbal intelligence. We examined the relationships between musicality (musical interest, creativity and expressivity), sociability (social-emotionality, social approach) and language comprehension in WS and typically developing (TD) controls. Findings suggest that emotion-expressivity through music in WS may be linked to their sensitivity and responsivity to emotions of others, whereas general interest in music may be related to greater linguistic capacity in TD individuals. Musicality and sociability may be more closely related in WS relative than in typical development; implications for future interventions for this neurodevelopmental condition will be discussed. PMID:24151530

Musicality Correlates With Sociability and Emotionality in Williams Syndrome.

PubMed

Ng, Rowena; Lai, Philip; Levitin, Daniel J; Bellugi, Ursula

2013-01-01

Williams Syndrome (WS) is a neurogenetic developmental disorder characterized by peaks and valleys of cognitive abilities. One peak that has been understudied is the affinity that many individuals with WS have toward music. It remains unknown whether their high levels of musical interest, skill and expressivity are related to their sociable personality or their verbal intelligence. We examined the relationships between musicality (musical interest, creativity and expressivity), sociability (social-emotionality, social approach) and language comprehension in WS and typically developing (TD) controls. Findings suggest that emotion-expressivity through music in WS may be linked to their sensitivity and responsivity to emotions of others, whereas general interest in music may be related to greater linguistic capacity in TD individuals. Musicality and sociability may be more closely related in WS relative than in typical development; implications for future interventions for this neurodevelopmental condition will be discussed.

Working Memory Impairment in People with Williams Syndrome: Effects of Delay, Task and Stimuli

ERIC Educational Resources Information Center

O'Hearn, Kirsten; Courtney, Susan; Street, Whitney; Landau, Barbara

2009-01-01

Williams syndrome (WS) is a neurodevelopmental disorder associated with impaired visuospatial representations subserved by the dorsal stream and relatively strong object recognition abilities subserved by the ventral stream. There is conflicting evidence on whether this uneven pattern in WS extends to working memory (WM). The present studies…

Ultrathin MoS2 and WS2 layers on silver nano-tips as electron emitters

NASA Astrophysics Data System (ADS)

Loh, Tamie A. J.; Tanemura, Masaki; Chua, Daniel H. C.

2016-09-01

2-dimensional (2D) inorganic analogues of graphene such as MoS2 and WS2 present interesting opportunities for field emission technology due to their high aspect ratio and good electrical conductivity. However, research on 2D MoS2 and WS2 as potential field emitters remains largely undeveloped compared to graphene. Herein, we present an approach to directly fabricate ultrathin MoS2 and WS2 onto Ag nano-tips using pulsed laser deposition at low temperatures of 450-500 °C. In addition to providing a layer of chemical and mechanical protection for the Ag nano-tips, the growth of ultrathin MoS2 and WS2 layers on Ag led to enhanced emission properties over that of pristine nano-tips due to a reduction of the effective barrier height arising from charge injection from Ag to the overlying MoS2 or WS2. For WS2 on Ag nano-tips, the phasic mixture was also an important factor influencing the field emission performance. The presence of 1T-WS2 at the metal-WS2 interface in a hybrid film of 2H/1T-WS2 leads to improvement in the field emission capabilities as compared to pure 2H-WS2 on Ag nano-tips.

A Comparative Study of Educational Provision for Children with Neurogenetic Syndromes: Parent and Teacher Survey

ERIC Educational Resources Information Center

Reilly, C.; Senior, J.; Murtagh, L.

2015-01-01

Background: A number of neurogenetic syndromes have a high association with special educational needs including fragile X syndrome (FXS), Prader-Willi syndrome (PWS), Williams syndrome (WS) and Velo-Cardio-Facial syndrome (VCFS). There is a paucity of research on educational provision for children affected by these syndromes. Method: Parents…

Genetic Mapping of Brain Plasticity Across Development in Williams Syndrome: ERP Markers of Face and Language Processing

PubMed Central

Mills, D. L.; Dai, L.; Fishman, I.; Yam, A.; Appelbaum, L. G.; Galaburda, A.; Bellugi, U.; Korenberg, J. R.

2014-01-01

In Williams Syndrome (WS), a known genetic deletion results in atypical brain function with strengths in face and language processing. We examined how genetic influences on brain activity change with development. In three studies, ERPs from large samples of children, adolescents, and adults with the full genetic deletion for WS were compared to typically developing controls, and two adults with partial deletions for WS. Studies 1 and 2 identified ERP markers of brain plasticity in WS across development. Study 3 suggested that in adults with partial deletions for WS, specific genes may be differentially implicated in face and language processing. PMID:24219698

Psychopathology in Williams Syndrome: The Effect of Individual Differences across the Life Span

ERIC Educational Resources Information Center

Dodd, Helen F.; Porter, Melanie A.

2009-01-01

This research aimed to comprehensively explore psychopathology in Williams syndrome (WS) across the life span and evaluate the relationship between psychopathology and age category (child or adult), gender, and cognitive ability. The parents of 50 participants with WS, ages 6-50 years, were interviewed using the Schedule for Affective Disorders…

An approach for scalable production of silver (Ag) decorated WS2 nanosheets

NASA Astrophysics Data System (ADS)

Sumesh, C. K.; Kapatel, Sanni; Chaudhari, Arti

2018-05-01

In the Present study we report the synthesis of Ag nanoparticles (NPs) decorated WS2 nanosheets by sonochemical exfoliation followed by simple chemical reduction process at room temperature. The morphology and microstructure of the as-synthesized Ag-WS2 nanocomposite were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and optical absorption (UV-Vis.) spectroscopy. X-ray and TEM analysis shows the presence of Ag with significant peak over 38.08°, 44.22°, 64.37° and 77.33° at 2θ angle for (111), (200), (220) and (311) respectively. The Ag nanoparticles are randomly distributed throughout the surface of the WS2 nanosheets without undergoing further oxidation during the formation of composites. The formation of Ag-WS2 nanocomposites shows a clear blue shift in the absorption as we obtained the characteristics absorption valleys at 456, 536 and 631 nm from the UV Vis spectroscopy analysis compared to pure WS2 nanosheets. Henceforth a facile method for the Ag decoration on WS2 nanosheets was put forward and briefly discussed. The proposed synthesis method is very promising for the low cost and large-scale synthesis of other noble metal incorporation TMDC compounds.

Fast-Response Single-Nanowire Photodetector Based on ZnO/WS2 Core/Shell Heterostructures.

PubMed

Butanovs, Edgars; Vlassov, Sergei; Kuzmin, Alexei; Piskunov, Sergei; Butikova, Jelena; Polyakov, Boris

2018-04-25

The surface plays an exceptionally important role in nanoscale materials, exerting a strong influence on their properties. Consequently, even a very thin coating can greatly improve the optoelectronic properties of nanostructures by modifying the light absorption and spatial distribution of charge carriers. To use these advantages, 1D/1D heterostructures of ZnO/WS 2 core/shell nanowires with a-few-layers-thick WS 2 shell were fabricated. These heterostructures were thoroughly characterized by scanning and transmission electron microscopy, X-ray diffraction, and Raman spectroscopy. Then, a single-nanowire photoresistive device was assembled by mechanically positioning ZnO/WS 2 core/shell nanowires onto gold electrodes inside a scanning electron microscope. The results show that a few layers of WS 2 significantly enhance the photosensitivity in the short wavelength range and drastically (almost 2 orders of magnitude) improve the photoresponse time of pure ZnO nanowires. The fast response time of ZnO/WS 2 core/shell nanowire was explained by electrons and holes sinking from ZnO nanowire into WS 2 shell, which serves as a charge carrier channel in the ZnO/WS 2 heterostructure. First-principles calculations suggest that the interface layer i-WS 2 , bridging ZnO nanowire surface and WS 2 shell, might play a role of energy barrier, preventing the backward diffusion of charge carriers into ZnO nanowire.

Electrophysiological Correlates of Semantic Processing in Williams Syndrome

ERIC Educational Resources Information Center

Pinheiro, Ana P.; Galdo-Alvarez, Santaigo; Sampaio, Adriana; Niznikiewicz, Margaret; Goncalves, Oscar F.

2010-01-01

Williams syndrome (WS), a genetic neurodevelopmental disorder due to microdeletion in chromosome 7, has been described as a syndrome with an intriguing socio-cognitive phenotype. Cognitively, the relative preservation of language and face processing abilities coexists with severe deficits in visual-spatial tasks, as well as in tasks involving…

Brief Report: Major Depressive Disorder with Psychotic Features in Williams Syndrome--A Case Series

ERIC Educational Resources Information Center

Valdes, Francisca; Keary, Christopher J.; Mullett, Jennifer E.; Palumbo, Michelle L.; Waxler, Jessica L.; Pober, Barbara R.; McDougle, Christopher J.

2018-01-01

Descriptions of individuals with Williams syndrome (WS) and co-morbid major depressive disorder (MDD) with psychotic features have not appeared in the literature. In addition to reviewing previous reports of psychotic symptoms in persons with WS, this paper introduces clinical histories and therapeutic management strategies for three previously…

CoP/WS2 nanoflake heterostructures as efficient electrocatalysts for significant improvement in hydrogen evolution activity

NASA Astrophysics Data System (ADS)

Chen, Yajie; Kang, Chuanhong; Wang, Ruihong; Ren, Zhiyu; Fu, Huiying; Xiao, Yuting; Tian, Guohui

2018-06-01

The CoP/WS2 nanoflake composites were synthesized via the sulfuration and subsequent phosphidation using the pre-prepared WO2.72 nanowires as precursors. Originally, WO2.72 nanowires were prepared and followed by sulfuration to obtain WS2 nanoflakes. The as-prepared WS2 nanoflakes were used as substrates, on which the Co3O4 nanoparticles were uniformly anchored to construct the Co3O4/WS2 nanoflakes. Finally, the Co3O4/WS2 composites were subjected to phosphidation and in-situ converted into CoP/WS2 nanoflakes. Because of the dual functionalities of both CoP and WS2, the abundant interfaces as well as their synergy, the CoP/WS2 nanoflakes exhibited much higher electrocatalytic activity, smaller overpotential (-81 mV), lower Tafel slope (62 mV decade-1), and higher stability toward hydrogen-evolution reaction than those for the single CoP and WS2.

Adaptive behavior in Chinese children with Williams syndrome

PubMed Central

2014-01-01

Background Williams syndrome (WS) is a neurodevelopmental disease characterized by compelling psychological phenotypes. The symptoms span multiple cognitive domains and include a distinctive pattern of social behavior. The goal of this study was to explore adaptive behavior in WS patients in China. Methods We conducted a structured interview including the Infants-Junior Middle School Students Social-life Abilities Scale in three participant groups: children with WS (n = 26), normally-developing children matched for mental age (MA, n = 30), and normally-developing children matched for chronological age (CA, n = 40). We compared the mean scores for each domain between the three groups. Results Children with WS had more siblings than children in the two control groups. The educational level of the caregivers of WS children was lower than that of the control children. We found no differences in locomotion, work skill, socialization, or self-management between the WS and MA groups. WS children obtained higher scores of self-dependence (df = 54, Z = −2.379, p = 0.017) and had better communication skills (df = 54, Z = −2.222, p = 0.026) compared with MA children. The CA children achieved higher scores than the WS children for all dimensions of adaptive behavior. Conclusions WS children have better adaptive behavior skills regarding communication and self-dependence than normal children matched for mental age. Targeted intervention techniques should be designed to promote social development in this population. PMID:24708693

Personal Space Regulation in Williams Syndrome: The Effect of Familiarity.

PubMed

Lough, Emma; Flynn, Emma; Riby, Deborah M

2016-10-01

Personal space refers to a protective barrier that we strive to maintain around our body. We examined personal space regulation in young people with Williams syndrome (WS) and their typically developing, chronological age-matched peers using a parent report questionnaire and a stop-distance paradigm. Individuals with WS were reported by their parents to be more likely to violate the personal space of others, and indeed they maintained a shorter interpersonal distance in the stop-distance paradigm. Interestingly, WS individuals failed to regulate their personal space based on the familiarity of the person they were interacting with. Findings are discussed in relation to the wider social profile associated with WS, and the possible impact of atypical personal space regulation on social vulnerability.

Neurocranial morphology and growth in Williams syndrome.

PubMed

Axelsson, Stefan; Kjaer, Inger; Heiberg, Arvid; Bjørnland, Tore; Storhaug, Kari

2005-02-01

Williams syndrome (WS) is a rare congenital neurodevelopmental disorder with distinctive facial features, cardiovascular abnormalities, short stature, mental retardation, and behaviour and cognitive characteristics. The aim of this study was to describe the neurocranial morphology and growth in a group of 62 individuals with WS. The neurocranium was analysed on lateral cephalograms and comparisons were made with neurocranial standards from longitudinal data derived from the Oslo University Craniofacial Growth Archive. The size and morphology of the neurocranium in WS subjects differed from controls. Females as a group showed greater differences than males. The posterior cranial base length was shorter in both WS males and females, and the anterior cranial base length was shorter in WS females whereas it was close to normal in the WS male group. The cranial base angle was, however, not different from the control groups. A flattening was seen in the superior aspect of the parietal bone in both WS males and females. In the posterior part of the neurocranium, the prominence of the occipital bone was larger than in the control groups, which was also reflected in a larger total length of the neurocranium. The thickness of the frontal and occipital bones was considerably greater than in the control group. The deviant size and morphology of the neurocranium in WS subjects was already established in the youngest age group and maintained throughout the observation period. The growth pattern of the neurocranium in WS subjects seemed to be similar to that of the control groups, except in a few individuals.

Orientation and Affective Expression Effects on Face Recognition in Williams Syndrome and Autism

ERIC Educational Resources Information Center

Rose, Fredric E.; Lincoln, Alan J.; Lai, Zona; Ene, Michaela; Searcy, Yvonne M.; Bellugi, Ursula

2007-01-01

We sought to clarify the nature of the face processing strength commonly observed in individuals with Williams syndrome (WS) by comparing the face recognition ability of persons with WS to that of persons with autism and to healthy controls under three conditions: Upright faces with neutral expressions, upright faces with varying affective…

Exploring the Williams Syndrome Face-Processing Debate: The Importance of Building Developmental Trajectories

ERIC Educational Resources Information Center

Karmiloff-Smith, Annette; Thomas, Michael; Annaz, Dagmara; Humphreys, Kate; Ewing, Sandra; Brace, Nicola; Van Duuren, Mike; Pike, Graham; Grice, Sarah; Campbell, Ruth

2004-01-01

Background: Face processing in Williams syndrome (WS) has been a topic of heated debate over the past decade. Initial claims about a normally developing ("intact") face-processing module were challenged by data suggesting that individuals with WS used a different balance of cognitive processes from controls, even when their behavioural scores fell…

Characterisation of Sleep Problems in Children with Williams Syndrome

ERIC Educational Resources Information Center

Annaz, Dagmara; Hill, Catherine M.; Ashworth, Anna; Holley, Simone; Karmiloff-Smith, Annette

2011-01-01

Sleep is critical to optimal daytime functioning, learning and general health. In children with established developmental disorders sleep difficulties may compound existing learning difficulties. The purpose of the present study was to evaluate the prevalence and syndrome specificity of sleep problems in Williams syndrome (WS), a…

Language and emotional abilities in children with Williams syndrome and children with autism spectrum disorder: similarities and differences

PubMed Central

Lacroix, Agnès; Famelart, Nawelle; Guidetti, Michèle

2016-01-01

Williams syndrome (WS) is a genetic disease with a relatively homogeneous profile: relatively well-preserved language, impaired cognitive activities, and hypersociability. Autism spectrum disorder (ASD) refers to a group of individuals with impairments in aspects of communication and a particular pattern of language acquisition. Although ASD and WS are polar opposites when it comes to communication abilities (language and emotion) and social behavior, comparisons between WS and ASD are still rare in the literature. ASD and WS are both associated with general language and developmental delays. Difficulties in social interaction and general pragmatic difficulties are reported in both ASD and WS, but are more pervasive in ASD. Regarding facial emotion recognition, the two syndromes differ markedly in sensitivity to human faces. Despite the heterogeneity of these two groups, only a few studies with children have paid sufficient attention to participant recruitment and study design. A number of aspects need to be taken into account (eg, small age range, homogeneity of the subgroups, matching with typically developing children) if scientific results are to inform the design of intervention programs for children with neurodevelopmental disorders such as ASD and WS. PMID:29388584

Prosodic Abilities in Spanish and English Children with Williams Syndrome: A Cross-Linguistic Study

ERIC Educational Resources Information Center

Martinez-Castilla, Pastora; Stojanovik, Vesna; Setter, Jane; Sotillo, Maria

2012-01-01

The aim of this study was to compare the prosodic profiles of English- and Spanish-speaking children with Williams syndrome (WS), examining cross-linguistic differences. Two groups of children with WS, English and Spanish, of similar chronological and nonverbal mental age, were compared on performance in expressive and receptive prosodic tasks…

30 WS North Base Wind Study

NASA Technical Reports Server (NTRS)

Wheeler, Mark

2011-01-01

The 30 Weather Squadron (30 WS) is concerned about strong winds observed at their northern towers without advance warning. They state that terrain influences along the extreme northern fringes of Vandenberg Air Force Base (VAFB) make it difficult for forecasters to issue timely and accurate high wind warnings for northeasterly wind events. These events tend to occur during the winter or early spring when they are under the influence of the Great Basin high pressure weather regime. The Launch Weather Officers (LWOs) have seen these rapid wind increases in the current northern Towers 60, 70 and 71 in excess of their 35 kt operational warning threshold. For this task, the 30 WS requested the Applied Meteorology Unit (AMU) analyze data from days when these towers reported winds in excess of 35 kt and determine if there were any precursors in the observations that would allow the LWOs to better forecast and warn their operational customers for these wind events. The 30 WS provided wind tower data for the cool season (October - March) from the period January 2004-March 20 IO. The AMU decoded and evaluated the wind tower data for 66 days identified by the 30 WS as having high-wind events. Out of the 66 event days, only 30 had wind speed observations of > or =35 kt from at least one of the three northern towers. The AMU analyzed surface and upper air charts to determine the synoptic conditions for each event day along with tower peak wind speed and direction time series and wind rose charts for all 30 event days. The analysis revealed a trend on all event days in which the tower winds shifted to the northeast for a period of time before the first recorded > or =35 kt wind speed. The time periods for the 30 event days ranged from 20 minutes to several hours, with a median value of 110 minutes. This trend, if monitored, could give the 30 WS forecasters a precursor to assist in issuing an operational warning before a high wind event occurs. The AMU recommends developing a

Developmental Course of Conversational Behaviour of Children with 22q11.2 Deletion Syndrome and Williams Syndrome

ERIC Educational Resources Information Center

Van Den Heuvel, Ellen; Botting, Nicola; Boudewijns, Inge; Manders, Eric; Swillen, Ann; Zink, Inge

2017-01-01

This study investigated three conversational subskills in children with 22q11.2 deletion syndrome (22q11.2DS, n = 8, ages 7-13) and Williams syndrome (WS, n = 8, ages 6-12). The researchers re-evaluated these subskills after 18 to 24 months and compared them to those of peers with idiopathic intellectual disability (IID) and IID and comorbid…

Tuning Coupling Behavior of Stacked Heterostructures Based on MoS2, WS2, and WSe2

PubMed Central

Wang, Fang; Wang, Junyong; Guo, Shuang; Zhang, Jinzhong; Hu, Zhigao; Chu, Junhao

2017-01-01

The interlayer interaction of vertically stacked heterojunctions is very sensitive to the interlayer spacing, which will affect the coupling between the monolayers and allow band structure modulation. Here, with the aid of density functional theory (DFT) calculations, an interesting phenomenon is found that MoS2-WS2, MoS2-WSe2, and WS2-WSe2 heterostructures turn into direct-gap semiconductors from indirect-gap semiconductors with increasing the interlayer space. Moreover, the electronic structure changing process with interlayer spacing of MoS2-WS2, MoS2-WSe2, and WS2-WSe2 is different from each other. With the help of variable-temperature spectral experiment, different electronic transition properties of MoS2-WS2, MoS2-WSe2, and WS2-WSe2 have been demonstrated. The transition transformation from indirect to direct can be only observed in the MoS2-WS2 heterostructure, as the valence band maximum (VBM) at the Γ point in the MoS2-WSe2 and WS2-WSe2 heterostructure is less sensitive to the interlayer spacing than those from the MoS2-WS2 heterostructure. The present work highlights the significance of the temperature tuning in interlayer coupling and advance the research of MoS2-WS2, MoS2-WSe2, and WS2-WSe2 based device applications. PMID:28303932

Atypical Verbal Communication Pattern According to Others' Attention in Children with Williams Syndrome

ERIC Educational Resources Information Center

Asada, Kosuke; Tomiwa, Kiyotaka; Okada, Masako; Itakura, Shoji

2010-01-01

Children with Williams syndrome (WS) have been reported to often face problems in daily communication and to have deficits in their pragmatic language abilities. To test this hypothesis, we examined whether children with WS could modify their verbal communication according to others' attention in order to share what they did. The children with WS…

How executive functions are related to intelligence in Williams syndrome.

PubMed

Osório, Ana; Cruz, Raquel; Sampaio, Adriana; Garayzábal, Elena; Martínez-Regueiro, Rocío; Gonçalves, Óscar F; Carracedo, Ángel; Fernández-Prieto, Montse

2012-01-01

Williams syndrome is characterized by impairments in executive functions (EFs). However, it remains unknown how distinct types of EFs relate to intelligence in this syndrome. The present study analyzed performance on working memory, inhibiting and shifting, and its links to IQ in a sample of 17 individuals with WS, and compared them with a group of 17 typically developing individuals matched on chronological age and gender. In conclusion, our results suggest that working memory, inhibiting, and shifting relate differently to intelligence in WS as well as in typical development, with working memory being the EF most closely related to intelligence in both groups. Notably, the magnitude of the associations between the three EFs and IQ was substantially higher in the WS group than in the TD group, bringing further confirmation to the notion that frontal lobe impairments may produce a general compromise of several EFs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synthesis and Performance of Tungsten Disulfide/Carbon (WS2/C) Composite as Anode Material

NASA Astrophysics Data System (ADS)

Yuan, Zhengyong; Jiang, Qiang; Feng, Chuanqi; Chen, Xiao; Guo, Zaiping

2018-01-01

The precursors of an amorphous WS2/C composite were synthesized by a simple hydrothermal method using Na2WO4·2H2O and CH3CSNH2 as raw materials, polyethylene glycol as dispersant, and glucose as the carbon source. The as-synthesized precursors were further annealed at a low temperature in flowing argon to obtain the final materials (WS2/C composite). The structure and morphology of the WS2/C composite were characterized by x-ray diffraction, x-ray photoelectron spectroscopy, and scanning electron microscopy. The electrochemical properties were tested by galvanostatic charge/discharge testing and alternating current (AC) impedance measurements. The results show that the as-prepared amorphous WS2/C composite features both high specific capacity and good cycling performance at room temperature within the potential window from 3.0 V to 0.01 V (versus Li+/Li) at current density of 100 mAg-1. The achieved initial discharge capacity was 1080 mAhg-1, and 786 mAhg-1 was retained after 170 cycles. Furthermore, the amorphous WS2/C composite exhibited a lower charge/discharge plateau than bare WS2, which is more beneficial for use as an anode. The cyclic voltammetry and AC impedance testing further confirmed the change in the plateau and the decrease in the charge transfer resistance in the WS2/C composite. The chemical formation process and the electrochemical mechanism of the WS2/C composite are also presented. The amorphous WS2/C composite can be used as a new anode material for future applications.

Anomalous sylvian fissure morphology in Williams syndrome.

PubMed

Eckert, Mark A; Galaburda, Albert M; Karchemskiy, Asya; Liang, Alyssa; Thompson, Paul; Dutton, Rebecca A; Lee, Agatha D; Bellugi, Ursula; Korenberg, Julie R; Mills, Debra; Rose, Fredric E; Reiss, Allan L

2006-10-15

The unusual sensitivity and attraction to auditory stimuli in people with Williams syndrome (WS) has been hypothesized to be the consequence of atypical development of brain regions surrounding the Sylvian fissure. Planum temporale surface area, which is determined in part by Sylvian fissure patterning, was examined in 42 WS and 40 control participants to determine if anomalous Sylvian fissure morphology is present in WS. WS participants had significantly reduced leftward asymmetry of the planum temporale compared to control participants, due to a significant expansion in the size of the right planum temporale. The increased right planum temporale size was largely due to WS participants (24%) who had a right hemisphere Sylvian fissure that coursed horizontally and failed to ascend into the parietal lobe. This sulcal pattern is unusual in the right hemisphere and is more commonly found in the left hemisphere of typically developing individuals. There were no control participants with this type of right hemisphere Sylvian fissure pattern. The right hemisphere Sylvian fissure sulcal patterns were also related to a measure of cortical complexity and the amount of right hemisphere occipital lobe volume, suggesting that intrinsic genetic influences leading to anomalous visual system development in WS have widespread influences on cortical morphology that are similar in manner to extrinsic embryonic visual system lesions.

Expecting the Worst: Observations of Reactivity to Sound in Young Children with Williams Syndrome

ERIC Educational Resources Information Center

Gallo, Frank J.; Klein-Tasman, Bonita P.; Gaffrey, Michael S.; Curran, Phillip

2008-01-01

The study examined behavioral reactions to sound, including startle eye blinks, in young children with Williams syndrome (WS) using video-based observational techniques. Participants were 21 children with WS and 20 children with other developmental disabilities of mixed etiology between the ages of 2.5 and 6. Groups were matched for chronological…

WS1: one more new Galactic bona fide luminous blue variable★

NASA Astrophysics Data System (ADS)

Kniazev, A. Y.; Gvaramadze, V. V.; Berdnikov, L. N.

2015-04-01

In this Letter, we report the results of spectroscopic and photometric monitoring of the candidate luminous blue variable (LBV) WS1, which was discovered in 2011 through the detection of a mid-infrared circular shell and follow-up optical spectroscopy of its central star. Our monitoring showed that WS1 brightened in the B, V and I bands by more than 1 mag during the last three years, while its spectrum revealed dramatic changes during the same time period, indicating that the star became much cooler. The light curve of WS1 demonstrates that the brightness of this star has reached maximum in 2013 December and then starts to decline. These findings unambiguously proved the LBV nature of WS1 and added one more member to the class of Galactic bona fide LBVs, bringing their number to sixteen (an updated census of these objects is provided).

Pulsed cathodoluminescence and Raman spectra of MoS{sub 2} and WS{sub 2} nanocrystals and their combination MoS{sub 2}/WS{sub 2} produced by self-propagating high-temperature synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bozheyev, Farabi, E-mail: farabi.bozheyev@gmail.com; National Nanolaboratory, al-Farabi Kazakh National University, 71 al-Farabi Ave., 050000 Almaty; Nazarbayev University Research and Innovation System, 53 Kabanbay Batyr St., 010000 Astana

2016-02-29

Molybdenum and tungsten disulfide nanoplates were produced by self-propagating high-temperature synthesis in argon atmosphere. This method provides an easy way to produce MoS{sub 2} and WS{sub 2} from nanoplates up to single- and several layers. The Raman peak intensities corresponding to in-plane E{sup 1}{sub 2g} and out-of-plane A{sub 1g} vibration modes and their shifts strongly depend on the thicknesses of the MoS{sub 2} and WS{sub 2} platelets indicating size-dependent scaling laws and properties. An electron beam irradiation of MoS{sub 2} and WS{sub 2} powders leads to an occurrence of pulsed cathodoluminescence (PCL) spectra at 575 nm (2.15 eV) and 550 nm (2.25 eV) characteristicmore » to their intrinsic band gaps. For the combination of MoS{sub 2} and WS{sub 2} nanopowders, a PCL shoulder at 430 nm (2.88 eV) was observed, which is explained by the radiative electron-hole recombination at the MoS{sub 2}/WS{sub 2} grain boundaries. The luminescence decay kinetics of the MoS{sub 2}/WS{sub 2} nanoplates appears to be slower than for individual MoS{sub 2} and WS{sub 2} platelets due to a spatial separation of electrons and holes at MoS{sub 2}/WS{sub 2} junction resulting in extension of recombination time.« less

There's that scary picture: attention bias to threatening scenes in Williams syndrome.

PubMed

Dodd, Helen F; Porter, Melanie A

2011-01-01

There is increasing evidence that Williams syndrome (WS) is associated with elevated anxiety that is non-social in nature, including generalised anxiety and fears. To date very little research has examined the cognitive processes associated with this anxiety. In the present research, attentional bias for non-social threatening images in WS was examined using a dot-probe paradigm. Participants were 16 individuals with WS aged between 13 and 34 years and two groups of typically developing controls matched to the WS group on chronological age and attentional control ability, respectively. The WS group exhibited a significant attention bias towards threatening images. In contrast, no bias was found for group matched on attentional control and a slight bias away from threat was found in the chronological age matched group. The results are contrasted with recent findings suggesting that individuals with WS do not show an attention bias for threatening faces and discussed in relation to neuroimaging research showing elevated amygdala activation in response to threatening non-social scenes in WS. Copyright © 2010 Elsevier Ltd. All rights reserved.

Pamidronate Rescue Therapy for Hypercalcemia in a Child With Williams Syndrome.

PubMed

Sanjad, Sami A; Aoun, Bilal; Yammine, Halim; Bassyouni, Amina; Karam, Pascale E

2018-01-01

A 15-month-old male infant diagnosed with Williams Syndrome (WS) was admitted with severe hypercalcemia and nephrocalcinosis. Intravenous hydration and furosemide failed to yield an appreciable and sustainable fall in serum calcium, while the injection of pamidronate achieved a significant decrease in serum calcium in a short period of time. This bisphosphonate could be considered as a second-line treatment for refractory hypercalcemia in WS.

Honing in on the Social Phenotype in Williams Syndrome Using Multiple Measures and Multiple Raters

ERIC Educational Resources Information Center

Klein-Tasman, Bonita P.; Li-Barber, Kirsten T.; Magargee, Erin T.

2011-01-01

The behavioral phenotype of Williams syndrome (WS) is characterized by difficulties with establishment and maintenance of friendships despite high levels of interest in social interaction. Here, parents and teachers rated 84 children with WS ages 4-16 years using two commonly-used measures assessing aspects of social functioning: the Social Skills…

Bifunctional Carbon-Dot-WS2 Nanorods for Photothermal Therapy and Cell Imaging.

PubMed

Nandi, Sukhendu; Bhunia, Susanta Kumar; Zeiri, Leila; Pour, Maayan; Nachman, Iftach; Raichman, Daniel; Lellouche, Jean-Paul Moshe; Jelinek, Raz

2017-01-18

Multifunctional nanoparticles have attracted significant interest as biomedical vehicles, combining diagnostic, imaging, and therapeutic properties. We describe herein the construction of new nanoparticle conjugates comprising WS 2 nanorods (NRs) coupled to fluorescent carbon dots (C-dots). We show that the WS 2 -C-dot hybrids integrate the unique physical properties of the two species, specifically the photothermal activity of the WS 2 NRs upon irradiation with near-infrared (NIR) light and the excitation-dependent luminescence emission of the C-dots. The WS 2 -C-dot NRs have been shown to be non-cytotoxic and have been successfully employed for multicolour cell imaging and targeted cell killing under NIR irradiation, pointing to their potential utilization as effective therapeutic vehicles. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Problem Behaviour and Psychosocial Functioning in Young Children with Williams Syndrome: Parent and Teacher Perspectives

ERIC Educational Resources Information Center

Klein-Tasman, B. P.; Lee, K.

2017-01-01

Background: There is sparse literature about problem behaviour in young children with Williams syndrome (WS) and little consideration of the perspectives of multiple respondents. Methods: Problem behaviour of 35 children with WS ages 2 to 6 was examined based on both parent and teacher report using the Achenbach preschool forms. Results: The most…

The proceedings of the 15th professional conference on Williams Syndrome.

PubMed

Walton, Jennifer R; Martens, Marilee A; Pober, Barbara R

2017-05-01

Williams Syndrome (WS) is a contiguous gene deletion disorder, caused by the deletion of approximately 26-28 genes from chromosome 7 (7q11.23). Individuals with WS have complex medical, developmental, and behavioral features, requiring multidisciplinary and interdisciplinary collaboration. Guidelines detailing the identification, evaluation, and monitoring of individuals with WS need clarification, especially for primary care providers who are first-line in their management. This report summarizes the proceedings of the 2016 Professional Conference on WS in Columbus, OH. Presentations were directed towards primary care providers and subspecialists, emphasizing evidence-based practices for treating the prevalent medical and behavioral features of WS. Included in this report are findings from a panel of cardiovascular experts discussing three case studies on treatment of hypertension and the use of sedation or anesthesia for non-cardiac procedures. Abstracts from individual expert presenters are included, covering various medical and behavioral topics, and providing updates in management of WS individuals. The following topics were discussed: differences in phenotypes of 7q11.23 deletion versus duplication, growth parameters, endocrine concerns, sleep difficulties, behaviors to monitor, and pharmacological options, the neurodevelopmental profile of WS individuals, and the importance of monitoring medical and behavioral concerns as WS individuals transition to adulthood. © 2017 Wiley Periodicals, Inc.

Large-area synthesis of high-quality and uniform monolayer WS2 on reusable Au foils

PubMed Central

Gao, Yang; Liu, Zhibo; Sun, Dong-Ming; Huang, Le; Ma, Lai-Peng; Yin, Li-Chang; Ma, Teng; Zhang, Zhiyong; Ma, Xiu-Liang; Peng, Lian-Mao; Cheng, Hui-Ming; Ren, Wencai

2015-01-01

Large-area monolayer WS2 is a desirable material for applications in next-generation electronics and optoelectronics. However, the chemical vapour deposition (CVD) with rigid and inert substrates for large-area sample growth suffers from a non-uniform number of layers, small domain size and many defects, and is not compatible with the fabrication process of flexible devices. Here we report the self-limited catalytic surface growth of uniform monolayer WS2 single crystals of millimetre size and large-area films by ambient-pressure CVD on Au. The weak interaction between the WS2 and Au enables the intact transfer of the monolayers to arbitrary substrates using the electrochemical bubbling method without sacrificing Au. The WS2 shows high crystal quality and optical and electrical properties comparable or superior to mechanically exfoliated samples. We also demonstrate the roll-to-roll/bubbling production of large-area flexible films of uniform monolayer, double-layer WS2 and WS2/graphene heterostructures, and batch fabrication of large-area flexible monolayer WS2 film transistor arrays. PMID:26450174

Exciton dynamics and annihilation in WS2 2D semiconductors.

PubMed

Yuan, Long; Huang, Libai

2015-04-28

We systematically investigate the exciton dynamics in monolayered, bilayered, and trilayered WS2 two-dimensional (2D) crystals by time-resolved photoluminescence (TRPL) spectroscopy. The exciton lifetime when free of exciton annihilation was determined to be 806 ± 37 ps, 401 ± 25 ps, and 332 ± 19 ps for WS2 monolayer, bilayer, and trilayer, respectively. By measuring the fluorescence quantum yields, we also establish the radiative and nonradiative lifetimes of the direct and indirect excitons. The exciton decay in monolayered WS2 exhibits a strong excitation density-dependence, which can be described using an exciton-exciton annihilation (two-particle Auger recombination) model. The exciton-exciton annihilation rate for monolayered, bilayered, and trilayered WS2 was determined to be 0.41 ± 0.02, (6.00 ± 1.09) × 10(-3) and (1.88 ± 0.47) × 10(-3) cm(2) s(-1), respectively. Notably, the exciton-exciton annihilation rate is two orders of magnitude faster in the monolayer than in the bilayer and trilayer. We attribute the much slower exciton-exciton annihilation rate in the bilayer and trilayer to reduced many-body interaction and phonon-assisted exciton-exciton annihilation of indirect excitons.

Characterizing associations and dissociations between anxiety, social, and cognitive phenotypes of Williams syndrome

PubMed Central

Ng, Rowena; Järvinen, Anna; Bellugi, Ursula

2014-01-01

Williams syndrome (WS) is a neurogenetic disorder known for its “hypersocial” phenotype and a complex profile of anxieties. The anxieties are poorly understood specifically in relation to the social-emotional and cognitive profiles. To address this gap, we employed a Wechsler intelligence test, the Brief Symptom Inventory, Beck Anxiety Inventory, and Salk Institute Sociability Questionnaire, to (1) examine how anxiety symptoms distinguish individuals with WS from typically developing (TD) individuals; and (2) assess the associations between three key phenotypic features of WS: intellectual impairment, social-emotional functioning, and anxiety. The results highlighted intensified neurophysiological symptoms and subjective experiences of anxiety in WS. Moreover, whereas higher cognitive ability was positively associated with anxiety in WS, the opposite pattern characterized the TD individuals. This study provides novel insight into how the three core phenotypic features associate/dissociate in WS, specifically in terms of the contribution of cognitive and emotional functioning to anxiety symptoms. PMID:24973548

Development of Novel Metaphor and Metonymy Comprehension in Typically Developing Children and Williams Syndrome

ERIC Educational Resources Information Center

Van Herwegen, Jo; Dimitriou, Dagmara; Rundblad, Gabriella

2013-01-01

This study investigated the development of novel metaphor and metonymy comprehension in both typically developing (TD) children and individuals with Williams syndrome (WS). Thirty-one TD children between the ages of 3;09 and 17;01 and thirty-four individuals with WS between the ages of 7;01 and 44 years old were administered a newly developed task…

Crataegus Special Extract WS 1442 Effects on eNOS and microRNA 155.

PubMed

Wang, Xinwen; Liang, Yan; Shi, Jian; Zhu, Hao-Jie; Bleske, Barry E

2018-04-16

Increased expression of microRNA 155 (miR-155) results in a decrease in endothelial nitric oxide synthase (eNOS) expression and impaired endothelial function. Factors that have been shown to increase expression of miR-155 may be mitigated by WS 1442, an extract of hawthorn leaves and flowers ( Crataegus special extract) that contains a range of pharmacologically active substances including oligomeric proanthocyanidins and flavonoids. The purpose of this study is to determine the effect of WS 1442 on the expression of miR-155 and eNOS in the presence of tumor necrosis factor (TNF- α ). Human umbilical vein endothelial cells (HUVECs) were studied after the exposure to TNF- α , with or without simvastatin (positive control) and WS 1442. The expression levels of eNOS, phosphorylated eNOS, and miR-155 in the different HUVEC treatment groups were determined by western blot and quantitative real-time polymerase chain reaction, respectively. To evaluate the effect of WS 1442 on the eNOS activity, the medium and intracellular nitrate/nitrite (NO) concentrations were also analyzed using a colorimetric Griess assay kit. The results demonstrated that TNF- α upregulated miR-155 expression and decreased eNOS expression and NO concentrations. WS 1442 also increased miR-155 expression and decreased eNOS expression but, unlike TNF- α , increased phosphorylated eNOS expression and NO concentrations. Surprisingly, WS 1442 increased miR-155 expression; however, WS 1442 mitigated the overall negative effect of miR-155 on decreasing eNOS expression by increasing expression of phosphorylated eNOS and resulting in an increase in NO concentrations. In the setting where miR-155 may be expressed, WS 1442 may offer vascular protection by increasing the expression of phosphorylated eNOS. Georg Thieme Verlag KG Stuttgart · New York.

Fluorescent 2D WS2 Nanosheets Bearing Chemical Affinity Elements for the Recognition of Glycated Hemoglobin.

PubMed

Yang, Jin-Kyoung; Lee, Hye-Rim; Hwang, In-Jun; Kim, Hye-In; Yim, DaBin; Kim, Jong-Ho

2018-05-14

It is required to exfoliate and functionalize 2D transition metal dichalcogenides (TMDs) in an aqueous solution for biological and medical applications. Herein, the approach for the simultaneous exfoliation and functionalization of 2D WS 2 nanosheets using boronic acid-modified poly(vinyl alcohol) (B-PVA) in an aqueous solution is reported, and the B-PVA-functionalized WS 2 nanosheets (B-PVA-WS 2 ) are exploited as a fluorescent biosensor for the detection of glycated hemoglobin, HbA1c. The synthetic B-PVA polymer facilitates the exfoliation and functionalization of WS 2 nanosheets from the bulk counterpart in the aqueous solution via a pulsed sonication process, resulting in fluorescent B-PVA-WS 2 nanohybrids with a specific recognition of HbA1c. The fluorescence of the B-PVA-WS 2 is quenched in the presence of HbA1c, whereas PVA-functionalized WS 2 (PVA-WS 2 ), not bearing boronic acid as a recognition moiety, shows no fluorescence changes upon the addition of the target. The B-PVA-WS 2 is able to selectively detect HbA1c at the concentration as low as 3.3 × 10 -8 m based on its specific fluorescence quenching. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Williams syndrome starts making sense

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashkenas, J.

1996-10-01

1996 may be marked as a transitional year in the study of Williams syndrome (WS), when the causes of this complex condition and a practical way to investigate began to come into focus. WS presents a remarkable collection of symptoms that affect blood vessels, growth, intelligence, and behavior. WS commonly leads to infantile hypercalcemia, retardation of growth, prematurely wrinkled skin, supraventricular aortic stenosis (SVAS), and sensitivity to loud noise. Children with this condition are often mentally retarded, with distinctive {open_quotes}elfin{close_quotes} facial features, a hoarse voice, and an {open_quotes}engaging{close_quotes} personality. Their cognitive deficits may be minimal or profound but typically involvemore » a specific pattern of strengths and weaknesses, with better-than-average face recognition but little ability to recognize how parts of patterns that they see fit into a whole. 36 refs.« less

Mathematical skill in individuals with Williams Syndrome: Evidence from a standardized mathematics battery

PubMed Central

O’Hearn, Kirsten; Landau, Barbara

2007-01-01

Williams syndrome (WS) is a developmental disorder associated with relatively spared verbal skills and severe visuospatial deficits. It has also been reported that individuals with WS are impaired at mathematics. We examined mathematical skills in persons with WS using the second edition of the Test of Early Mathematical Ability (TEMA-2), which measures a wide range of skills. We administered the TEMA-2 to 14 individuals with WS and 14 children matched individually for mental age on the matrices subtest of the Kaufman Brief Intelligence Test. There were no differences between groups on the overall scores on the TEMA-2. However, an item-by-item analysis revealed group differences. Participants with WS performed more poorly than controls when reporting which of two numbers was closest to a target number, a task thought to utilize a mental number line subserved by the parietal lobe, consistent with previous evidence showing parietal abnormalities in people with WS. In contrast, people with WS performed better than the control group at reading numbers, suggesting that verbal math skills may be comparatively strong in WS. These findings add to evidence that components of mathematical knowledge may be differentially damaged in developmental disorders. PMID:17482333

Mathematical skill in individuals with Williams syndrome: evidence from a standardized mathematics battery.

PubMed

O'Hearn, Kirsten; Landau, Barbara

2007-08-01

Williams syndrome (WS) is a developmental disorder associated with relatively spared verbal skills and severe visuospatial deficits. It has also been reported that individuals with WS are impaired at mathematics. We examined mathematical skills in persons with WS using the second edition of the Test of Early Mathematical Ability (TEMA-2), which measures a wide range of skills. We administered the TEMA-2 to 14 individuals with WS and 14 children matched individually for mental-age on the matrices subtest of the Kaufman Brief Intelligence Test. There were no differences between groups on the overall scores on the TEMA-2. However, an item-by-item analysis revealed group differences. Participants with WS performed more poorly than controls when reporting which of two numbers was closest to a target number, a task thought to utilize a mental number line subserved by the parietal lobe, consistent with previous evidence showing parietal abnormalities in people with WS. In contrast, people with WS performed better than the control group at reading numbers, suggesting that verbal math skills may be comparatively strong in WS. These findings add to evidence that components of mathematical knowledge may be differentially damaged in developmental disorders.

Writing abilities in intellectual disabilities: a comparison between Down and Williams syndrome.

PubMed

Varuzza, Cristiana; De Rose, Paola; Vicari, Stefano; Menghini, Deny

2015-02-01

Writing is a complex task that requires the integration of multiple cognitive, linguistic, and motor abilities. Until now, only a few studies investigated writing abilities in individuals with Intellectual Disability (ID). The aim of the present exploratory study was to provide knowledge on the organization of writing in two populations with ID, Down syndrome (DS) and Williams syndrome (WS), trying to disentangle different components of the process. A battery tapping diverse writing demands as low-level transcription skills as well as high-level writing skills was proposed to 13 individuals with WS, 12 individuals with DS and 11 mental-age-matched typically developing (TD) children. Results showed that the two groups with genetic syndromes did not differ from TD in writing a list of objects placed in bedroom, in the number of errors in the text composition, in a text copying task and in kind of errors made. However, in a word dictation task, individuals with DS made more errors than individuals with WS and TD children. In a pseudoword dictation task, both individuals with DS and WS showed more errors than TD children. Our results showed good abilities in individuals with ID in different aspects of writing, involving not only low-level transcription skills but also high-level composition skills. Contrary to the pessimistic view, considering individuals with ID vulnerable for failure, our results indicate that the presence of ID does not prevent the achievement of writing skills. Copyright © 2014 Elsevier Ltd. All rights reserved.

Syntax in Spanish-speaking children with Williams syndrome.

PubMed

Benítez-Burraco, Antonio; Garayzábal, Elena; Cuetos, Fernando

2016-01-01

The syntactic skills of Spanish-speaking children with Williams syndrome (WS) were assessed in different areas (phrase structure, recursion, and bound anaphora). Children were compared to typically-developing peers matched either in chronological age (CA-TD) or in verbal age (VA-TD). In all tasks children with WS performed significantly worse than CA-TD children, but similarly to VA-TD children. However, significant differences were observed in specific domains, particularly regarding sentences with cross-serial dependencies. At the same time, children with WS were less sensitive to syntactic constraints and exhibited a poorer knowledge of some functional words (specifically, of nonreflexive pronouns). A processing bottleneck or a computational constraint may account for this outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Parent Report of Antidepressant, Anxiolytic, and Antipsychotic Medication Use in Individuals with Williams Syndrome: Effectiveness and Adverse Effects

ERIC Educational Resources Information Center

Martens, Marilee A.; Seyfer, Daisha L.; Andridge, Rebecca R.; Foster, Jessica E. A.; Chowdhury, Monali; McClure, Kelsey E.; Coury, Daniel L.

2012-01-01

Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage…

Crataegus special extract WS 1442 increases force of contraction in human myocardium cAMP-independently.

PubMed

Schwinger, R H; Pietsch, M; Frank, K; Brixius, K

2000-05-01

The mode of action of Crataegus extracts in the treatment of heart failure is still under examination. WS 1442, a standardized special extract from Crataegus leaves with flowers, exerts direct positive inotropic effects. This study was designed to investigate the mode of inotropic action of WS 1442 in human myocardium from patients with congestive heart failure (left ventricular myocardium from explanted hearts; NYHA IV, n = 8) as well as in nonfailing controls (right auricular trabeculae from patients with coronary heart disease, n = 8). WS 1442 effectively displaced specifically bound 3H-ouabain but did not influence the activity of adenylate cyclase [control, + Gpp(NH)p (10(-4) microM) 3,500 pmol cyclic adenosine monophosphate (cAMP)/20 min). In isolated left ventricular papillary muscle strips, WS 1442 significantly increased the force of contraction [basal, 1.8+/-0.2 mN; WS 1442 (50 microg/ml), 2.4+/-0.1 mN (130%)] and improved the frequency-dependent force generation (0.5 vs. 2.5 Hz: control, +0.1+/-0.01 mN; WS 1442, +0.9+/-0.3 mN) even in failing human myocardium. In fura-2-loaded muscle strips (right atrial trabeculae), WS 1442 increased both the Ca2+-transient and force generation. These effects also were observed in the lipophilic ethyl acetate-soluble fraction A, enriched in flavone derivatives. In conclusion, these findings suggest a pharmacologic mechanism of WS 1442 similar to the cAMP-independent positive inotropic action of cardiac glycosides. In addition, WS 1442 improves the force-frequency relation in failing human myocardium.

Musical learning in children and adults with Williams syndrome.

PubMed

Lense, M; Dykens, E

2013-09-01

There is recent interest in using music making as an empirically supported intervention for various neurodevelopmental disorders due to music's engagement of perceptual-motor mapping processes. However, little is known about music learning in populations with developmental disabilities. Williams syndrome (WS) is a neurodevelopmental genetic disorder whose characteristic auditory strengths and visual-spatial weaknesses map onto the processes used to learn to play a musical instrument. We identified correlates of novel musical instrument learning in WS by teaching 46 children and adults (7-49 years) with WS to play the Appalachian dulcimer. Obtained dulcimer skill was associated with prior musical abilities (r = 0.634, P < 0.001) and visual-motor integration abilities (r = 0.487, P = 0.001), but not age, gender, IQ, handedness, auditory sensitivities or musical interest/emotionality. Use of auditory learning strategies, but not visual or instructional strategies, predicted greater dulcimer skill beyond individual musical and visual-motor integration abilities (β = 0.285, sr(2) = 0.06, P = 0.019). These findings map onto behavioural and emerging neural evidence for greater auditory-motor mapping processes in WS. Results suggest that explicit awareness of task-specific learning approaches is important when learning a new skill. Implications for using music with populations with syndrome-specific strengths and weakness will be discussed. © 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID.

MRI Assessment of Superior Temporal Gyrus in Williams Syndrome

PubMed Central

Sampaio, Adriana; Sousa, Nuno; Férnandez, Montse; Vasconcelos, Cristiana; Shenton, Martha E.; Gonçalves, Óscar F.

2009-01-01

Objective To evaluate volumes and asymmetry of superior temporal gyrus (STG) and correlate these measures with a neurocognitive evaluation of verbal performance in Williams syndrome (WS) and in a typically developing age-matched and sex-matched group. Background Despite initial claims of language strength in WS, recent studies suggest delayed language milestones. The STG is implicated in linguistic processing and is a highly lateralized brain region. Method Here, we examined STG volumes and asymmetry of STG in WS patients and in age-matched controls. We also correlated volume of STG with a subset of verbal measures. Magnetic resonance imaging scans were obtained on a GE 1.5-T magnet with 1.5-mm contiguous slices, and were used to measure whole gray matter, white matter, and cerebrospinal fluid volumes, and also STG volume. Results Results revealed significantly reduced intracranial volume in WS patients, compared with controls. Right and left STG were also significantly smaller in WS patients. In addition, compared with normal controls, a lack of normal left >right STG asymmetry was evident in WS. Also of note was the finding that, in contrast to controls, WS patients did not reveal a positive correlation between verbal intelligence quotient and left STG volume, which further suggests a disruption in this region of the brain. Conclusions In conclusion, atypical patterns of asymmetry and reduced STG volume in WS were observed, which may, in part, contribute to some of the linguistic impairments found in this cohort of WS patients. PMID:18797257

[Hereditary hypomelanocytoses: the role of PAX3, SOX10, MITF, SNAI2, KIT, EDN3 and EDNRB genes].

PubMed

Otręba, Michał; Miliński, Maciej; Buszman, Ewa; Wrześniok, Dorota; Beberok, Artur

2013-11-26

Hypo- and hyperpigmentation disorders are the most severe dermatological diseases observed in patients from all over the world. These disorders can be divided into melanoses connected with disorders of melanocyte function and melanocytoses connected with melanocyte development. The article presents some hereditary hypomelanocytoses, which are caused by abnormal melanoblast development, migration and proliferation as well as by abnormal melanocyte viability and proliferation. These disorders are represented by Waardenburg syndrome, piebaldism and Tietz syndrome, and are caused by different mutations of various or the same genes. The types of mutations comprise missense and nonsense mutations, frameshifts (in-frame insertions or deletions), truncating variations, splice alterations and non-stop mutations. It has been demonstrated that mutations of the same gene may cause different hypopigmentation syndromes that may have similar phenotypes. For example, mutations of the MITF gene cause Waardenburg syndrome type 2A as well as Tietz syndrome. It has also been demonstrated that mutations of different genes may cause an identical syndrome. For example, mutations of MITF, SNAI2 and SOX10 genes are observed in Waardenburg syndrome type II and mutations of EDNRB, EDN3 and SOX10 genes are responsible for Waardenburg syndrome type IV. In turn, mutation of the KIT gene and/or heterozygous deletion of the SNAI2 gene result in piebaldism disease. The knowledge of the exact mechanisms of pigmentary disorders may be useful in the development of new therapeutic approaches to their treatment.

32 CFR Appendix B to Part 45 - DD Form 214ws

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false DD Form 214ws B Appendix B to Part 45 National... CERTIFICATE OF RELEASE OR DISCHARGE FROM ACTIVE DUTY (DD FORM 214/5 SERIES) Pt. 45, App. B Appendix B to Part 45—DD Form 214ws EC23OC91.007 ...

An investigation into semantic and phonological processing in individuals with Williams syndrome.

PubMed

Lee, Cheryl S; Binder, Katherine S

2014-02-01

The current study examined semantic and phonological processing in individuals with Williams syndrome (WS). Previous research in language processing in individuals with WS suggests a complex linguistic system characterized by "deviant" semantic organization and differential phonological processing. Two experiments explored these representations in individuals with WS. The first experiment analyzed the relative typicality and frequency of participants' responses to a semantic and phonological fluency task. The second experiment tapped into online language processing through a semantic priming task and an online sentence reading task measuring the effects of word frequency. Thirteen participants with WS were matched to a group of participants on reading grade level and a group of participants on chronological age. The results of the semantic fluency task, semantic priming task, and word frequency task suggest that semantic organization in individuals with WS appears commensurate with their reading level rather than deviant. The pattern of results suggests that individuals with WS do not appear to have deviant semantic organization, while confirming that online tasks that tap into these processes are a promising direction in investigations that include atypically developing populations. These findings for the phonological tasks warrant further research into phonological processing in individuals with WS.

Anxiety in Williams Syndrome: The Role of Social Behaviour, Executive Functions and Change over Time

ERIC Educational Resources Information Center

Ng-Cordell, Elise; Hanley, Mary; Kelly, Alyssa; Riby, Deborah M.

2018-01-01

Anxiety is a prevalent mental health issue for individuals with Williams syndrome (WS). Relatively little is known about the developmental course of anxiety, or how it links with core features of WS, namely social and executive functioning (EF). In this study, parent-reports of anxiety were compared across a 4-year period (N = 17), and links…

Parent insights into atypicalities of social approach behaviour in Williams syndrome.

PubMed

Lough, E; Rodgers, J; Janes, E; Little, K; Riby, D M

2016-11-01

Individuals with Williams syndrome have been reported to show high levels of social interest and a desire to interact with others irrespective of their familiarity. This high social motivation, when combined with reduced intellectual capacity and a profile of atypical social behaviour, is important in terms of social vulnerability of individuals with the disorder. Therefore, social approach to unfamiliar people and the role of this behaviour within the Williams syndrome (WS) social phenotype warrant further research to inform social skills' intervention design. The current study used parent interviews (n = 21) to probe aspects of social behaviour and interactions with strangers, as well as the impact of such behaviour on the family. Using thematic analysis, it was possible to explore themes that emerged from the interviews, offering qualitatively rich insight into the variability of social approach behaviour in WS. Thematic analysis confirmed a significant desire to interact with strangers as well as a lack of awareness of appropriate social boundaries. However, parental reports about their child's social approach behaviour varied considerably. The within-syndrome variability of the sample was emphasised in parental reports of their child's personality characteristics (e.g. levels of impulsiveness), as well as the level of parental supervision employed. These in-depth parent insights can help target the needs of individuals with WS and emphasise that an individual approach to intervention will be essential because of the heterogeneity of the WS social profile. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Attention Bias to Emotional Faces Varies by IQ and Anxiety in Williams Syndrome.

PubMed

McGrath, Lauren M; Oates, Joyce M; Dai, Yael G; Dodd, Helen F; Waxler, Jessica; Clements, Caitlin C; Weill, Sydney; Hoffnagle, Alison; Anderson, Erin; MacRae, Rebecca; Mullett, Jennifer; McDougle, Christopher J; Pober, Barbara R; Smoller, Jordan W

2016-06-01

Individuals with Williams syndrome (WS) often experience significant anxiety. A promising approach to anxiety intervention has emerged from cognitive studies of attention bias to threat. To investigate the utility of this intervention in WS, this study examined attention bias to happy and angry faces in individuals with WS (N = 46). Results showed a significant difference in attention bias patterns as a function of IQ and anxiety. Individuals with higher IQ or higher anxiety showed a significant bias toward angry, but not happy faces, whereas individuals with lower IQ or lower anxiety showed the opposite pattern. These results suggest that attention bias interventions to modify a threat bias may be most effectively targeted to anxious individuals with WS with relatively high IQ.

Attention bias to emotional faces varies by IQ and anxiety in Williams syndrome

PubMed Central

McGrath, Lauren M.; Oates, Joyce M.; Dai, Yael G.; Dodd, Helen F.; Waxler, Jessica; Clements, Caitlin C.; Weill, Sydney; Hoffnagle, Alison; Anderson, Erin; MacRae, Rebecca; Mullett, Jennifer; McDougle, Christopher J.; Pober, Barbara R.; Smoller, Jordan W.

2016-01-01

Individuals with Williams syndrome (WS) often experience significant anxiety. A promising approach to anxiety intervention has emerged from cognitive studies of attention bias to threat. To investigate the utility of this intervention in WS, this study examined attention bias to happy and angry faces in individuals with WS (N=46). Results showed a significant difference in attention bias patterns as a function of IQ and anxiety. Individuals with higher IQ or higher anxiety showed a significant bias toward angry, but not happy faces, whereas individuals with lower IQ or lower anxiety showed the opposite pattern. These results suggest that attention bias interventions to modify a threat bias may be most effectively targeted to anxious individuals with WS with relatively high IQ. PMID:26886469

A kinematic analysis of visually-guided movement in Williams syndrome.

PubMed

Hocking, Darren R; Rinehart, Nicole J; McGinley, Jennifer L; Moss, Simon A; Bradshaw, John L

2011-02-15

Previous studies have reported that people with the neurodevelopmental disorder Williams syndrome exhibit difficulties with visuomotor control. In the current study, we examined the extent to which visuomotor deficits were associated with movement planning or feedback-based on-line control. We used a variant of the Fitts' reciprocal aiming task on a computerized touchscreen in adults with WS, IQ-matched individuals with Down syndrome (DS), and typically developing controls. By manipulating task difficulty both as a function of target size and amplitude, we were able to vary the requirements for accuracy to examine processes associated with dorsal visual stream and cerebellar functioning. Although a greater increase in movement time as a function of task difficulty was observed in the two clinical groups with WS and DS, greater magnitude in the late kinematic components of movement-specifically, time after peak velocity-was revealed in the WS group during increased demands for accuracy. In contrast, the DS group showed a greater speed-accuracy trade-off with significantly reduced and more variable endpoint accuracy, which may be associated with cerebellar deficits. In addition, the WS group spent more time stationary in the target when task-related features reflected a higher level of difficulty, suggestive of specific deficits in movement planning. Our results indicate that the visuomotor coordination deficits in WS may reflect known impairments of the dorsal stream, but may also indicate a role for the cerebellum in dynamic feed-forward motor control. Copyright © 2010 Elsevier B.V. All rights reserved.

Green synthesis route for WS2 nanosheets using water intercalation

NASA Astrophysics Data System (ADS)

Jha, Ravindra; Santra, Sumita; Guha, Prasanta Kumar

2016-09-01

The exfoliation of layered materials has attracted a lot of attention in recent times. In this report, we have exfoliated WS2 in deionized water (without using any chemical solvents, surfactants, etc) using the thermal coefficient mismatch between WS2 and H2O along with other anomalous properties of water, such as the formation of five-, six- and seven-ring structures while freezing. Two different green synthesis routes have been proposed for WS2 exfoliation. We call them the ‘hard’ and ‘soft’ quenching methods. The nanosheets were investigated using different characterization tools and we found the exfoliation of the bulk into <4 layers with an average lateral dimension of 200 nm. The exfoliation method is unique in the sense of producing pristine nanosheets due to the absence of any organic solvents, which are difficult to remove.

Preparation and improved photocatalytic activity of mesoporous WS{sub 2} using combined hydrothermal-evaporation induced self-assembly method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vattikuti, S.V. Prabhakar, E-mail: vsvprabu@gmail.com; Byon, Chan, E-mail: cbyon@ynu.ac.kr; Reddy, Ch. Venkata

2016-03-15

Highlights: • One-step method for synthesis of mesoporous WS{sub 2} was proposed. • Role of CTAB surfactant on formation of mesoporous WS{sub 2} was elucidated. • Possible growth mechanism of the mesoporous structure is also reported. • 0.1 wt% mesoporous WS{sub 2} catalyst exhibited high photocatalytic activity under UV light. - Abstract: In this paper, we report mesoporous WS{sub 2} nanosheets with a crystalline network that were synthesized using CTAB as a structure-directing agent via self-assembly induced by hydrothermal and thermal evaporation. Powder X-ray diffraction, Raman spectra, and high-resolution X-ray photoelectron spectroscopy results confirmed the formation of WS{sub 2} structures.more » Scanning electron microscopy and transmission electron microscopy were used to observe the as-prepared mesoporous frameworks. The mesoporous WS{sub 2} nanosheets have a surface area of 197 m{sup 2} g{sup −1}. A possible growth mechanism is reported for these mesoporous WS{sub 2} nanosheets. The mesoporous WS{sub 2} nanosheets demonstrate high photocatalytic activity. Among different concentrations, 0.1 wt% mesoporous WS{sub 2} shows superior catalytic activity compared to pristine WS{sub 2} nanosheets.« less

Parent and Self-Report Ratings on the Perceived Levels of Social Vulnerability of Adults with Williams Syndrome.

PubMed

Lough, Emma; Fisher, Marisa H

2016-11-01

The current study took a multi-informant approach to compare parent to self-report ratings of social vulnerability of adults with Williams syndrome (WS). Participants included 102 pairs of adults with WS and their parents. Parents completed the Social Vulnerability Questionnaire and adults with WS completed an adapted version of the questionnaire. Parents consistently reported higher levels of social vulnerability for their son/daughter than the individual with WS reported, with the exception of emotional abuse. The lower ratings of social vulnerability by adults with WS, compared to their parents, offer new information about their insight into their own vulnerability. These findings highlight the importance of teaching self-awareness as a part of a multi-informant approach to interventions designed to target social vulnerability.

Self-lubricating Al-WS2 composites for efficient and greener tribological parts.

PubMed

Niste, Vlad Bogdan; Ratoi, Monica; Tanaka, Hiroyoshi; Xu, Fang; Zhu, Yanqiu; Sugimura, Joichi

2017-11-07

Due to their mechanical and physical properties, aluminium alloys possess wide potential in the automotive industry, particularly in hot reciprocating applications such as pistons for diesel and petrol engines. WS 2 particle-reinforced composites could bring further improvements by reducing friction and wear between moving parts. Reducing friction improves efficiency by lowering energy/fuel use, ultimately leading to lower greenhouse gas emissions, while antiwear properties can prolong component life. This study compares for the first time the tribological performance of powder metallurgy-consolidated Al composites reinforced with either IF- or 2H-WS 2 particles, so as to elucidate their mechanism of action in test conditions similar to those encountered in engine applications. The composites were tested in lubricated reciprocating contacts against AISI52100 steel balls and the impact of WS 2 could be seen at both 25 and 100 °C. The reduced friction and wear at ambient temperature is due to the predominantly physical mechanism of action of WS 2 , while the best antiwear performance is measured at elevated (standard operating engine) temperatures that promote the chemical reaction of WS 2 with the aluminium matrix. The investigation focused on studying the wear tracks/scars and the tribofilms generated on the composite and ball with optical profilometry, SEM, XPS and Auger spectroscopy.

Effect of Musical Experience on Verbal Memory in Williams Syndrome: Evidence from a Novel Word Learning Task

ERIC Educational Resources Information Center

Martens, Marilee A.; Jungers, Melissa K.; Steele, Anita L.

2011-01-01

Williams syndrome (WS) is a neurogenetic developmental disorder characterized by an increased affinity for music, deficits in verbal memory, and atypical brain development. Music has been shown to improve verbal memory in typical individuals as well as those with learning difficulties, but no studies have examined this relationship in WS. The aim…

Atypical verbal communication pattern according to others' attention in children with Williams syndrome.

PubMed

Asada, Kosuke; Tomiwa, Kiyotaka; Okada, Masako; Itakura, Shoji

2010-01-01

Children with Williams syndrome (WS) have been reported to often face problems in daily communication and to have deficits in their pragmatic language abilities. To test this hypothesis, we examined whether children with WS could modify their verbal communication according to others' attention in order to share what they did. The children with WS and typically developing (TD) children were asked to accomplish tasks as quickly as possible while the experimenter was attending to or not attending to them during and after their accomplishment. The results showed that although TD children verbalized more when they were not attended to than attended to, children with WS verbalized more when they were attended to than not attended to. The results indicate that children with WS may have deficits in attention-sharing communication, suggesting a part of their pragmatic abilities is impaired. Copyright 2009 Elsevier Ltd. All rights reserved.

A Comparison of Behavioral and Emotional Characteristics in Children with Autism, Prader-Willi Syndrome, and Williams Syndrome

ERIC Educational Resources Information Center

Dimitropoulos, Anastasia; Ho, Alan Y.; Klaiman, Cheryl; Koenig, Kathy; Schultz, Robert T.

2009-01-01

In order to investigate unique and shared characteristics and to determine factors predictive of group classification, quantitative comparisons of behavioral and emotional problems were assessed using the Developmental Behavior Checklist (DBC-P) and the Vineland Adaptive Behavior Scales in autistic disorder, Williams syndrome (WS), and…

Growth and microstructural evolution of WS2 nanostructures with tunable field and light modulated electrical transport

NASA Astrophysics Data System (ADS)

Kumar, Pawan; Balakrishnan, Viswanath

2018-04-01

We report CVD growth of WS2 nanostructures with the ability to control the evolution of 1D to 2D microstructural changes for light and field effect transistor applications. Detailed mechanistic growth sequences from WO3 nanorod to nanotube, monolayer and pyramidal structures of WS2 has been achieved using atmospheric pressure chemical vapor deposition (APCVD). Electron microscopy and Raman spectroscopy analysis showed the growth evolution of different nanostructures and their formation mechanism. Location specific growth of different WS2 nanostructures can be achieved by drop casting dispersed WO3 nanorods on required substrate. Layer dependent photoluminescence (PL) properties of WS2 indicate the effect of quantum confinement induced radiative recombination and enhanced PL intensity in monolayer WS2 provides suitability for nanoscale photodetector application. The fabricated device shows light as well as field modulated switching at ultra-low biased voltage in hybrid WS2 nanostructure that contains 1D (nanotube)-2D (flake) interface. The demonstrated aspects of CVD growth and hybrid device characteristics provide opportunities to tune electrical transport of WS2 nanostructures at low active power.

Genetic Analyses of a Three Generation Family Segregating Hirschsprung Disease and Iris Heterochromia

PubMed Central

Cheng, Guo; Firmato de Almeida, Manoel; So, Man-Ting; Sham, Pak-Chung; Cherny, Stacey S.; Tam, Paul Kwong-Hang; Garcia-Barceló, Maria-Mercè

2013-01-01

We present the genetic analyses conducted on a three-generation family (14 individuals) with three members affected with isolated-Hirschsprung disease (HSCR) and one with HSCR and heterochromia iridum (syndromic-HSCR), a phenotype reminiscent of Waardenburg-Shah syndrome (WS4). WS4 is characterized by pigmentary abnormalities of the skin, eyes and/or hair, sensorineural deafness and HSCR. None of the members had sensorineural deafness. The family was screened for copy number variations (CNVs) using Illumina-HumanOmni2.5-Beadchip and for coding sequence mutations in WS4 genes (EDN3, EDNRB, or SOX10) and in the main HSCR gene (RET). Confocal microscopy and immunoblotting were used to assess the functional impact of the mutations. A heterozygous A/G transition in EDNRB was identified in 4 affected and 3 unaffected individuals. While in EDNRB isoforms 1 and 2 (cellular receptor) the transition results in the abolishment of translation initiation (M1V), in isoform 3 (only in the cytosol) the replacement occurs at Met91 (M91V) and is predicted benign. Another heterozygous transition (c.-248G/A; -predicted to affect translation efficiency-) in the 5′-untranslated region of EDN3 (EDNRB ligand) was detected in all affected individuals but not in healthy carriers of the EDNRB mutation. Also, a de novo CNVs encompassing DACH1 was identified in the patient with heterochromia iridum and HSCR Since the EDNRB and EDN3 variants only coexist in affected individuals, HSCR could be due to the joint effect of mutations in genes of the same pathway. Iris heterochromia could be due to an independent genetic event and would account for the additional phenotype within the family. PMID:23840513

Facilitating complex shape drawing in Williams syndrome and typical development.

PubMed

Hudson, Kerry D; Farran, Emily K

2013-07-01

Individuals with Williams syndrome (WS) produce drawings that are disorganised, likely due to an inability to replicate numerous spatial relations between parts. This study attempted to circumvent these drawing deficits in WS when copying complex combinations of one, two and three shapes. Drawing decisions were reduced by introducing a number of facilitators, for example, by using distinct colours and including facilitatory cues on the response sheet. Overall, facilitation improved drawing in the WS group to a comparable level of accuracy as typically developing participants (matched for non-verbal ability). Drawing accuracy was greatest in both groups when planning demands (e.g. starting location, line lengths and changes in direction) were reduced by use of coloured figures and providing easily distinguished and clearly grouped facilitatory cues to form each shape. This study provides the first encouraging evidence to suggest that drawing of complex shapes in WS can be facilitated; individuals with WS might be receptive to remediation programmes for drawing and handwriting. Copyright © 2013 Elsevier Ltd. All rights reserved.

Amygdala response to faces parallels social behavior in Williams syndrome

PubMed Central

Snyder, Abraham Z.; Haist, Frank; Raichle, Marcus E.; Bellugi, Ursula; Stiles, Joan

2009-01-01

Individuals with Williams syndrome (WS), a genetically determined disorder, show relatively strong face-processing abilities despite poor visuospatial skills and depressed intellectual function. Interestingly, beginning early in childhood they also show an unusually high level of interest in face-to-face social interaction. We employed functional magnetic resonance imaging (fMRI) to investigate physiological responses in face-sensitive brain regions, including ventral occipito-temporal cortex and the amygdala, in this unique genetic disorder. Participants included 17 individuals with WS, 17 age- and gender-matched healthy adults (chronological age-matched controls, CA) and 17 typically developing 8- to 9-year-old children (developmental age controls, DA). While engaged in a face discrimination task, WS participants failed to recruit the amygdala, unlike both CA and DA controls. WS fMRI responses in ventral occipito-temporal cortex, however, were comparable to those of DA controls. Given the integral role of the amygdala in social behavior, the failure of WS participants to recruit this region during face processing may be a neural correlate of the abnormally high sociability that characterizes this disorder. PMID:19633063

Accelerometer-determined physical activity and walking capacity in persons with Down syndrome, Williams syndrome and Prader-Willi syndrome.

PubMed

Nordstrøm, Marianne; Hansen, Bjørge Herman; Paus, Benedicte; Kolset, Svein Olav

2013-12-01

In this study we describe by use of accelerometers the total physical activity (PA), intensity pattern and walking capacity in 87 persons age 16-45 years with Down syndrome (DS), Williams syndrome (WS) and Prader-Willi syndrome (PWS). Participants were recruited from all over Norway, and lived either with their parents or in community residences with support. On average the participants generated 294 counts per minute (cpm) or 6712 steps per day, with most of the day spent in sedentary activity, 522 min/day, followed by 212 min/day in light PA, 71 min/day in lifestyle activity and 27 min/day in moderate-to-vigorous physical activity (MVPA). Inactivity was prevalent, as only 12% meet the current Nordic recommendations for PA. When compared, no differences for total physical activity or time in MVPA were observed between the three groups. However, participant with DS spent a mean of 73 min/day less and 43 min/day less in sedentary activities compared to participants with PWS and WS, respectively, (p=0.011, 95% CI: -10.9; -80.1). In addition the DS-group spent a mean of 66 min/day more in light PA than the PWS-group and 41 min/day more than the WS-group, (p<0.001, 95% CI: 29.3; 79.7). Participants with PWS spent on average 30 min/day less in lifestyle activities compared to both participants with DS and WS, (p<0.001, 95% CI: -14.2; -45.4). No association between total PA and BMI were observed. Males were more active than females across all diagnoses. Males accumulated on average 85 counts per minutes more than females, (p=0.002, 95% CI: 33.3; 136.7), 2137 more steps per day, (p=0.002, 95% CI: 778; 3496). The mean walking capacity during six-minutes was 507 m (SD 112 m) for males and 466 m (SD 88 m) for females. Distance walked during testing decreased with 33.6 m when comparing normal or underweight participants to overweight participants, and 78.1 m when comparing overweight to obese participants (p<0.001 95% CI: -40.4; -85.8). When adjusted for BMI no differences in

Social functioning and autonomic nervous system sensitivity across vocal and musical emotion in Williams syndrome and autism spectrum disorder.

PubMed

Järvinen, Anna; Ng, Rowena; Crivelli, Davide; Neumann, Dirk; Arnold, Andrew J; Woo-VonHoogenstyn, Nicholas; Lai, Philip; Trauner, Doris; Bellugi, Ursula

2016-01-01

Both Williams syndrome (WS) and autism spectrum disorders (ASD) are associated with unusual auditory phenotypes with respect to processing vocal and musical stimuli, which may be shaped by the atypical social profiles that characterize the syndromes. Autonomic nervous system (ANS) reactivity to vocal and musical emotional stimuli was examined in 12 children with WS, 17 children with ASD, and 20 typically developing (TD) children, and related to their level of social functioning. The results of this small-scale study showed that after controlling for between-group differences in cognitive ability, all groups showed similar emotion identification performance across conditions. Additionally, in ASD, lower autonomic reactivity to human voice, and in TD, to musical emotion, was related to more normal social functioning. Compared to TD, both clinical groups showed increased arousal to vocalizations. A further result highlighted uniquely increased arousal to music in WS, contrasted with a decrease in arousal in ASD and TD. The ASD and WS groups exhibited arousal patterns suggestive of diminished habituation to the auditory stimuli. The results are discussed in the context of the clinical presentation of WS and ASD. © 2015 Wiley Periodicals, Inc.

How Executive Functions Are Related to Intelligence in Williams Syndrome