title: Genetic and phenotypic heterogeneity in Chinese patients with Waardenburg syndrome type II.
abstract: Waardenburg Syndrome (WS) is an autosomal-dominant disorder characterized by sensorineural hearing loss and pigmentary abnormalities of the eyes, hair, and skin. Microphthalmia-associated transcription factor (MITF) gene mutations account for about 15% of WS type II (WS2) cases. To date, fewer than 40 different MITF gene mutations have been identified in human WS2 patients, and few of these were of Chinese descent. In this study, we report clinical findings and mutation identification in the MITF gene of 20 Chinese WS2 patients from 14 families. A high level of clinical variability was identified. Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients. Five affected individuals (5/20, 25.0%) had numerous brown freckles on the face, trunk, and limb extremities. Mutation screening of the MITF gene identified five mutations: c.20A>G, c.332C>T, c.647_649delGAA, c.649A>G, and c.763C>T. The total mutational frequency of the MITF gene was 21.4% (3/14), which is significantly higher than the 15.0% observed in the fair-skinned WS2 population. Our results indicate that MITF mutations are relatively common among Chinese WS2 patients.
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
authors.forename: Shuzhi
authors.initials: S
authors.lastname: Yang
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Dongyang
authors.initials: D
authors.lastname: Kang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Weiyan
authors.initials: W
authors.lastname: Yang
authors.forename: Chengyong
authors.initials: C
authors.lastname: Zhou
authors.forename: Shiming
authors.initials: S
authors.lastname: Yang
authors.forename: Huijun
authors.initials: H
authors.lastname: Yuan
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D019295:Computational Biology; D004252:DNA Mutational Analysis; D018740:Genetic Heterogeneity; D006319:Hearing Loss, Sensorineural / Q000473:pathology; D006801:Humans; D007499:Iris Diseases / Q000473:pathology; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D010859:Pigmentation Disorders / Q000473:pathology; D014849:Waardenburg Syndrome / Q000235:genetics* / Q000473:pathology*
chemical_list: C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor