title: Exome sequencing reveals novel BCS1L mutations in siblings with hearing loss and hypotrichosis.
abstract: As a powerful tool to identify the molecular pathogenesis of Mendelian disorders, exome sequencing was used to identify the genetic basis of two siblings with hearing loss and hypotrichosis and clarify the diagnosis. No pathogenic mutations in GJB2, GJB3 and GJB6 genes were found in the siblings. By analysis of exome of the proband, we identified a novel missense (p.R306C) mutation and a nonsense (p.R186*) mutation in the BCS1L gene. Mutations were confirmed by Sanger sequencing. The siblings were compound heterozygotes, and the inheritance mode of autosomal recessive was postulated. BCS1L is the causative gene of Björnstad syndrome, which is characterized by sensorineural hearing loss and pili torti. The longitudinal gutters along the hair shaft were found by scanning electron microscopy in our patient. Therefore the diagnosis of Björnstad syndrome was eventually made for the patients. Our study extends the phenotypic spectrum of Björnstad syndrome and highlights the clinical applicability of exome sequencing as a diagnostic tool for atypical Mendelian disorders.
authors.affiliation: Department of Dermatology, Qilu Hospital of Shandong University (Qingdao), Qingdao 266035, China; Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Peking-Tsinghua Center for Life Sciences, Beijing 100871, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Duo
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China.
authors.forename: Zhimiao
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China; Peking-Tsinghua Center for Life Sciences, Beijing 100871, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China; Peking-Tsinghua Center for Life Sciences, Beijing 100871, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Zhao
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Dai
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xuanzhu
authors.initials: X
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China; Peking-Tsinghua Center for Life Sciences, Beijing 100871, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Qilu Hospital of Shandong University, Jinan 250012, China. Electronic address: tzldyx2010@sina.com.
authors.forename: Zhanli
authors.initials: Z
authors.lastname: Tang
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000293:Adolescent; D002648:Child; D018389:Codon, Nonsense; D000072259:Connexin 26; D017630:Connexins; D004252:DNA Mutational Analysis; D014450:Electron Transport Complex III / Q000235:genetics*; D005260:Female; D006201:Hair Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D034381:Hearing Loss / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics; D008297:Male; D028361:Mitochondrial Diseases / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D020125:Mutation, Missense
chemical_list: C435491:BCS1L protein, human; D018389:Codon, Nonsense; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D000074183:ATPases Associated with Diverse Cellular Activities; D014450:Electron Transport Complex III
keywords: BCS1L gene; Björnstad syndrome; Exome sequencing; Hearing loss; Hypotrichosis