title: A molecular analysis of the yemenite deaf-blind hypopigmentation syndrome: SOX10 dysfunction causes different neurocristopathies.
abstract: The Yemenite deaf-blind hypopigmentation syndrome was first observed in a Yemenite sister and brother showing cutaneous hypopigmented and hyperpigmented spots and patches, microcornea, coloboma and severe hearing loss. A second case, observed in a girl with similar skin symptoms and hearing loss but without microcornea or coloboma, was reported as a mild form of this syndrome. Here we show that a SOX10 missense mutation is responsible for the mild form, resulting in a loss of DNA binding of this transcription factor. In contrast, no SOX10 alteration could be found in the other, severe case of the Yemenite deaf-blind hypopigmentation syndrome. Based on genetic, clinical, molecular and functional data, we suggest that these two cases represent two different syndromes. Moreover, as mutations of the SOX10 transcription factor were previously described in Waardenburg-Hirschsprung disease, these results show that SOX10 mutations cause various types of neurocristopathy.
authors.affiliation: Génétique Moléculaire et Physiopathologie, INSERM U468 et Laboratoire de Biochimie et Génétique Moléculaire, AP-HP, Hôpital Henri Mondor, 94010 Créteil Cedex, France.
authors.forename: N
authors.initials: N
authors.lastname: Bondurand
authors.forename: K
authors.initials: K
authors.lastname: Kuhlbrodt
authors.forename: V
authors.initials: V
authors.lastname: Pingault
authors.forename: J
authors.initials: J
authors.lastname: Enderich
authors.forename: M
authors.initials: M
authors.lastname: Sajus
authors.forename: N
authors.initials: N
authors.lastname: Tommerup
authors.forename: M
authors.initials: M
authors.lastname: Warburg
authors.forename: R C
authors.initials: RC
authors.lastname: Hennekam
authors.forename: A P
authors.initials: AP
authors.lastname: Read
authors.forename: M
authors.initials: M
authors.lastname: Wegner
authors.forename: M
authors.initials: M
authors.lastname: Goossens
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D019465:Craniofacial Abnormalities / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000235:genetics*; D051863:Host Cell Factor C1; D006801:Humans; D017496:Hypopigmentation / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000032:analysis; D050811:Octamer Transcription Factor-1; D018807:Polymorphism, Single-Stranded Conformational; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary; D055757:SOXE Transcription Factors; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015006:Yemen
chemical_list: D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D006609:High Mobility Group Proteins; D051863:Host Cell Factor C1; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D014157:Transcription Factors