title: A de novo SOX10 mutation causing severe type 4 Waardenburg syndrome without Hirschsprung disease.
abstract: Type 4 Waardenburg syndrome represents a well define entity caused by neural crest derivatives anomalies (melanocytes, intrinsic ganglion cells, central, autonomous and peripheral nervous systems) leading, with variable expressivity, to pigmentary anomalies, deafness, mental retardation, peripheral neuropathy, and Hirschsprung disease. Autosomal dominant mode of inheritance is prevalent when Sox10 gene mutation is identified. We report the natural history of a child who presented with synophrys, vivid blue eye, deafness, bilateral complete semicircular canals agenesis with mental retardation, subtle signs for peripheral neuropathy and lack of Hirschsprung disease. SOX10 gene sequencing identified "de novo" splice site mutation (c.698-2A > C). The present phenotype and the genotype findings underline the wide spectrum of SOX10 gene implication in unusual type 4 Waardenburg syndrome patient.
authors.affiliation: Hôpital Universitaire des Enfants Reine Fabiola, ULB, Pediatric Clinical Genetics, Brussels, Belgium. yves.sznajer@ulb.ac.be
authors.forename: Yves
authors.initials: Y
authors.lastname: Sznajer
authors.forename: Cristina
authors.initials: C
authors.lastname: Coldéa
authors.forename: Françoise
authors.initials: F
authors.lastname: Meire
authors.forename: Isabelle
authors.initials: I
authors.lastname: Delpierre
authors.forename: Tayeb
authors.initials: T
authors.lastname: Sekhara
authors.forename: Renaud L
authors.initials: RL
authors.lastname: Touraine
mesh_terms: D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005838:Genotype; D006609:High Mobility Group Proteins / Q000235:genetics*; D006627:Hirschsprung Disease / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D055757:SOXE Transcription Factors; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics*; D014849:Waardenburg Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D014157:Transcription Factors