title: Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4.
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.
authors.affiliation: INSERM U841, Institut Mondor de Recherche Biomedicale, Département de Génétique, Université Paris 12, Paris, France. nadege.bondurand@creteil.inserm.fr
authors.forename: Nadege
authors.initials: N
authors.lastname: Bondurand
authors.forename: Florence
authors.initials: F
authors.lastname: Dastot-Le Moal
authors.forename: Laure
authors.initials: L
authors.lastname: Stanchina
authors.forename: Nathalie
authors.initials: N
authors.lastname: Collot
authors.forename: Viviane
authors.initials: V
authors.lastname: Baral
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marlin
authors.forename: Tania
authors.initials: T
authors.lastname: Attie-Bitach
authors.forename: Irina
authors.initials: I
authors.lastname: Giurgea
authors.forename: Laurent
authors.initials: L
authors.lastname: Skopinski
authors.forename: William
authors.initials: W
authors.lastname: Reardon
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.forename: Anis
authors.initials: A
authors.lastname: Echaieb
authors.forename: Marilyn
authors.initials: M
authors.lastname: Lackmy-Port-Lis
authors.forename: Renaud
authors.initials: R
authors.lastname: Touraine
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.forename: Veronique
authors.initials: V
authors.lastname: Pingault
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D005799:Genes, Dominant; D006579:Heterozygote; D006609:High Mobility Group Proteins / Q000235:genetics*; D006627:Hirschsprung Disease / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D055757:SOXE Transcription Factors; D014157:Transcription Factors / Q000235:genetics*; D014849:Waardenburg Syndrome / Q000145:classification / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D014157:Transcription Factors