Zhang Jie, Duo Lina, Lin Zhimiao, Wang Huijun, Yin Jinghua, Cao Xu, Zhao Jiahui, Dai Lanlan, Liu Xuanzhu, Zhang Jianguo, Yang Yong, Tang Zhanli
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.
Gene. 2015 Jul 15;566(1):84-8. doi: 10.1016/j.gene.2015.04.039. Epub 2015 Apr 18.
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.
作为一种用于识别孟德尔疾病分子发病机制的强大工具，外显子组测序被用于确定两名患有听力损失和毛发稀少症的兄弟姐妹的遗传基础，并明确诊断。在这两名兄弟姐妹中未发现GJB2、GJB3和GJB6基因的致病突变。通过对先证者外显子组的分析，我们在BCS1L基因中鉴定出一个新的错义突变（p.R306C）和一个无义突变（p.R186*）。通过桑格测序证实了这些突变。这两名兄弟姐妹为复合杂合子，推测其遗传模式为常染色体隐性遗传。BCS1L是比约恩斯塔德综合征的致病基因，其特征为感音神经性听力损失和扭曲发。通过扫描电子显微镜在我们的患者中发现了沿毛干的纵向沟槽。因此最终对这些患者做出了比约恩斯塔德综合征的诊断。我们的研究扩展了比约恩斯塔德综合征的表型谱，并突出了外显子组测序作为非典型孟德尔疾病诊断工具的临床适用性。
