title: Homozygous and heterozygous inheritance of PAX3 mutations causes different types of Waardenburg syndrome.
abstract: Type I Waardenburg syndrome (WS-I) is an auditory-pigmentary syndrome caused by heterozygous loss of function mutations in the PAX3 gene. Klein-Waardenburg syndrome (WS-III) is a very rare condition and represents an extreme presentation of WS-I, additionally associated with musculoskeletal abnormalities. We present an 18-months old Turkish child with typical Klein-Waardenburg syndrome (WS) including dystopia canthorum, partial albinism, and upper-limb defects. The child was born to a consanguineous couple and both parents had WS-I. We screened the entire coding region of the PAX3 gene for mutations and identified a novel missense mutation, Y90H, within the paired box domain of PAX3. Both parents were heterozygous for the mutation and the proposita was homozygous. This is the third report of a homozygous PAX3 mutation causing the WS-III phenotype. Molecular analysis of four additional Turkish families with variable clinical expression of WS-I identified two missense mutations, one splice-site mutation, and one small insertion in the PAX3 gene.
authors.affiliation: Division of Medical Genetics, Child Health Institute, Istanbul University, Istanbul, Turkey. wollnik@superonline.com
authors.forename: Bernd
authors.initials: B
authors.lastname: Wollnik
authors.forename: Turgut
authors.initials: T
authors.lastname: Tukel
authors.forename: Oya
authors.initials: O
authors.lastname: Uyguner
authors.forename: Asadollah
authors.initials: A
authors.lastname: Ghanbari
authors.forename: Hulya
authors.initials: H
authors.lastname: Kayserili
authors.forename: Melike
authors.initials: M
authors.lastname: Emiroglu
authors.forename: Memnune
authors.initials: M
authors.lastname: Yuksel-Apak
mesh_terms: D000328:Adult; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D010375:Pedigree; D010641:Phenotype; D014157:Transcription Factors; D014849:Waardenburg Syndrome / Q000235:genetics* / Q000503:physiopathology
chemical_list: D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse