Display Settings:

Format

Send to:

Choose Destination
Am J Hum Genet. 2007 Dec;81(6):1169-85. Epub 2007 Oct 22.

Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4.

Author information

  • 1INSERM U841, Institut Mondor de Recherche Biomedicale, Département de Génétique, Université Paris 12, Paris, France. nadege.bondurand@creteil.inserm.fr

Abstract

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.

PMID:
17999358
[PubMed - indexed for MEDLINE]
PMCID:
PMC2276340
Free PMC Article

Images from this publication.See all images (5)Free text

Figure  1. 
Figure  2. 
Figure  3. 
Figure  4. 
Figure  5. 
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk