Document Detail

Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4.
MedLine Citation:
PMID:  17999358     Owner:  NLM     Status:  MEDLINE    
Waardenburg syndrome (WS) is an auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair and skin. Depending on additional symptoms, WS is classified into four subtypes, WS1-WS4. Absence of additional features characterizes WS2. The association of facial dysmorphic features defines WS1 and WS3, whereas the association with Hirschsprung disease (aganglionic megacolon) characterizes WS4, also called "Waardenburg-Hirschsprung disease." Mutations within the genes MITF and SNAI2 have been identified in WS2, whereas mutations of EDN3, EDNRB, and SOX10 have been observed in patients with WS4. However, not all cases are explained at the molecular level, which raises the possibility that other genes are involved or that some mutations within the known genes are not detected by commonly used genotyping methods. We used a combination of semiquantitative fluorescent multiplex polymerase chain reaction and fluorescent in situ hybridization to search for SOX10 heterozygous deletions. We describe the first characterization of SOX10 deletions in patients presenting with WS4. We also found SOX10 deletions in WS2 cases, making SOX10 a new gene of WS2. Interestingly, neurological phenotypes reminiscent of that observed in WS4 (PCWH syndrome [peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, WS, and Hirschsprung disease]) were observed in some WS2-affected patients with SOX10 deletions. This study further characterizes the molecular complexity and the close relationship that links the different subtypes of WS.
Nadege Bondurand; Florence Dastot-Le Moal; Laure Stanchina; Nathalie Collot; Viviane Baral; Sandrine Marlin; Tania Attie-Bitach; Irina Giurgea; Laurent Skopinski; William Reardon; Annick Toutain; Pierre Sarda; Anis Echaieb; Marilyn Lackmy-Port-Lis; Renaud Touraine; Jeanne Amiel; Michel Goossens; Veronique Pingault
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-22
Journal Detail:
Title:  American journal of human genetics     Volume:  81     ISSN:  1537-6605     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-13     Completed Date:  2007-12-13     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1169-85     Citation Subset:  IM    
INSERM U841, Institut Mondor de Recherche Biomedicale, Département de Génétique, Université Paris 12, Paris, France.
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MeSH Terms
DNA-Binding Proteins / genetics*
Gene Deletion*
Genes, Dominant
High Mobility Group Proteins / genetics*
Hirschsprung Disease / genetics
SOXE Transcription Factors
Transcription Factors / genetics*
Waardenburg's Syndrome / classification,  genetics*
Reg. No./Substance:
0/DNA-Binding Proteins; 0/High Mobility Group Proteins; 0/SOX10 protein, human; 0/SOXE Transcription Factors; 0/Transcription Factors

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