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Exome sequencing reveals novel BCS1L mutations in siblings with hearing loss and hypotrichosis.
Gene. 2015 Jul 15; 566(1):84-8.GENE

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+Show Affiliations

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.Peking-Tsinghua Center for Life Sciences, Beijing 100871, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China.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.Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China.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.Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China.BGI-Shenzhen, Shenzhen 518083, China.BGI-Shenzhen, Shenzhen 518083, China.BGI-Shenzhen, Shenzhen 518083, China.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.Department of Dermatology, Qilu Hospital of Shandong University, Jinan 250012, China. Electronic address: tzldyx2010@sina.com.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25895478

Citation

Zhang, Jie, et al. "Exome Sequencing Reveals Novel BCS1L Mutations in Siblings With Hearing Loss and Hypotrichosis." Gene, vol. 566, no. 1, 2015, pp. 84-8.
Zhang J, Duo L, Lin Z, et al. Exome sequencing reveals novel BCS1L mutations in siblings with hearing loss and hypotrichosis. Gene. 2015;566(1):84-8.
Zhang, J., Duo, L., Lin, Z., Wang, H., Yin, J., Cao, X., Zhao, J., Dai, L., Liu, X., Zhang, J., Yang, Y., & Tang, Z. (2015). Exome sequencing reveals novel BCS1L mutations in siblings with hearing loss and hypotrichosis. Gene, 566(1), 84-8. https://doi.org/10.1016/j.gene.2015.04.039
Zhang J, et al. Exome Sequencing Reveals Novel BCS1L Mutations in Siblings With Hearing Loss and Hypotrichosis. Gene. 2015 Jul 15;566(1):84-8. PubMed PMID: 25895478.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exome sequencing reveals novel BCS1L mutations in siblings with hearing loss and hypotrichosis. AU - Zhang,Jie, AU - Duo,Lina, AU - Lin,Zhimiao, AU - Wang,Huijun, AU - Yin,Jinghua, AU - Cao,Xu, AU - Zhao,Jiahui, AU - Dai,Lanlan, AU - Liu,Xuanzhu, AU - Zhang,Jianguo, AU - Yang,Yong, AU - Tang,Zhanli, Y1 - 2015/04/18/ PY - 2014/12/18/received PY - 2015/03/19/revised PY - 2015/04/11/accepted PY - 2015/4/22/entrez PY - 2015/4/22/pubmed PY - 2015/7/28/medline KW - BCS1L gene KW - Björnstad syndrome KW - Exome sequencing KW - Hearing loss KW - Hypotrichosis SP - 84 EP - 8 JF - Gene JO - Gene VL - 566 IS - 1 N2 - 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. SN - 1879-0038 UR - https://wwww.unboundmedicine.com/medline/citation/25895478/Exome_sequencing_reveals_novel_BCS1L_mutations_in_siblings_with_hearing_loss_and_hypotrichosis_ DB - PRIME DP - Unbound Medicine ER -