title: Molecular etiology and genotype-phenotype correlation of Chinese Han deaf patients with type I and type II Waardenburg Syndrome.
abstract: Waardenburg syndrome (WS) characterized by sensorineural hearing loss and pigmentary abnormalities is genetically heterogeneous and phenotypically variable. This study investigated the molecular etiology and genotype-phenotype correlation of WS in 36 Chinese Han deaf probands and 16 additional family members that were clinically diagnosed with WS type I (WS1, n = 8) and type II (WS2, n = 42). Mutation screening of six WS-associated genes detected PAX3 mutations in 6 (86%) of the 7 WS1 probands. Among the 29 WS2 probands, 13 (45%) and 10 (34%) were identified with SOX10 and MITF mutations, respectively. Nineteen of the 26 detected mutations were novel. In WS2 probands whose parental DNA samples were available, de novo mutations were frequently seen for SOX10 mutations (7/8) but not for MITF mutations (0/5, P = 0.005). Excessive freckle, a common feature of WS2 in Chinese Hans, was frequent in WS2 probands with MITF mutations (7/10) but not in those with SOX10 mutations (0/13, P = 4.9 × 10-4). Our results showed that mutations in SOX10 and MITF are two major causes for deafness associated with WS2. These two subtypes of WS2 can be distinguished by the high de novo rate of the SOX10 mutations and the excessive freckle phenotype exclusively associated with the MITF mutations.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.|Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Otology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.|Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Taizhou People's Hospital, Jiangsu Province, China.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Pang
authors.affiliation: High School Affiliated to Fudan University, Shanghai, China.
authors.forename: Yechen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.|Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.|Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.|Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D019295:Computational Biology / Q000379:methods; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D055757:SOXE Transcription Factors / Q000235:genetics; D014849:Waardenburg Syndrome / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D051739:Microphthalmia-Associated Transcription Factor; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors