title: Screening of MITF and SOX10 regulatory regions in Waardenburg syndrome type 2.
abstract: 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.
authors: INSERM, U955, equipe11, Créteil, France.
authors: Viviane
authors: V
authors: Baral
authors: Asma
authors: A
authors: Chaoui
authors: Yuli
authors: Y
authors: Watanabe
authors: Michel
authors: M
authors: Goossens
authors: Tania
authors: T
authors: Attie-Bitach
authors: Sandrine
authors: S
authors: Marlin
authors: Veronique
authors: V
authors: Pingault
authors: Nadege
authors: N
authors: Bondurand
mesh_terms: D000293:Adolescent; D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D055757:SOXE Transcription Factors / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics; D014849:Waardenburg Syndrome / Q000235:genetics*
chemical_list: D051739:Microphthalmia-Associated Transcription Factor; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors