中华皮肤科杂志 ›› 2020, Vol. 53 ›› Issue (2): 93-97.doi: 10.35541/cjd.20190740

• 论著 • 上一篇    下一篇

Bjornstad综合征致病BCS1L基因的新发突变位点研究

李思源    刘婷婷    杨淑霞    马圣清    杨勇   

  1. 北京大学第一医院皮肤科  北京市皮肤病分子诊断重点实验室  国家皮肤与免疫疾病临床医学研究中心  100034
    杨勇现在中国医学科学院  北京协和医学院  皮肤病医院遗传病中心工作，南京  210042
  • 收稿日期:2019-07-12 修回日期:2019-11-15 发布日期:2020-02-01
  • 通讯作者: 杨勇 E-mail:yyang@pumcderm.cams.cn
  • 基金资助:
    国家自然科学基金杰出青年基金（81425020）

Identification of a novel mutation in the BCS1L gene causing Bjornstad syndrome

Li Siyuan, Liu Tingting, Yang Shuxia, Ma Shengqing, Yang Yong   

  1. Department of Dermatology （and Venerology）, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, National Clinical Research Center for Skin and Immune Diseases, Beijing 100034, China 
  • Received:2019-07-12 Revised:2019-11-15 Published:2020-02-01
  • Contact: Yang Yong E-mail:yyang@pumcderm.cams.cn
  • Supported by:
    National Science Foundation for Distinguished Young Scholars（81425020）

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摘要： 【摘要】 目的 检测1例以先天性头发扭曲和感音性听力丧失为主要表现的Bj-rnstad综合征（扭曲发综合征）患者的致病基因BCS1L的突变情况。方法 收集患者临床资料，提取患者及其父母的外周血DNA，PCR扩增BCS1L基因全部外显子及侧翼序列并进行Sanger测序，测序结果与正常序列进行比对；取患者头发进行扫描电镜检查。结果 患者BCS1L基因存在2处突变：①第4号外显子上存在杂合无义突变，即第144位密码子CGA→TGA，导致其编码氨基酸序列由精氨酸变为终止密码子（p.R144*），此为BCS1L基因突变导致Bj-rnstad综合征新发现的致病突变位点，属国际首例；②第8号外显子上存在杂合错义突变，即第306位密码子CGC→CAC，导致其编码氨基酸序列由精氨酸变为组氨酸（p.R306H）。患者母亲仅在BCS1L基因第4号外显子发生c.430 C>T杂合突变（p.R144*），患者父亲仅在BCS1L基因第8号外显子发生c.917 G>A杂合突变（p.R306H）。扫描电镜显示，患者发干以不规则的间隔出现扁平、沟槽和沿长轴的扭曲。结论 首次报道BCS1L基因第144位密码子CGA→TGA导致的编码终止为该基因突变导致Bj-rnstad综合征的新发突变位点，BCS1L基因复合杂合突变与患者的临床表现相关，基因检测有助于Bj-rnstad综合征的诊断。

关键词: 线粒体疾病； 基因, 线粒体； DNA突变分析； Bj-rnstad综合征； BCS1L基因

Abstract: 【Abstract】 Objective To identify gene mutations in the BCS1L gene in a patient with Bj-rnstad syndrome mainly manifesting as congenital pili torti and sensorineural hearing loss. Methods Clinical data were collected and DNA was extracted from the peripheral blood of the patient and her parents. All the exons and their flanking sequences of the BCS1L gene were amplified by PCR followed by Sanger sequencing, and the sequencing results were compared with the normal sequences. A few hairs were collected from the patient, and examined by the scanning electron microscope. Results There were two mutations in BCS1L gene in the patient, i.e., a heterozygous nonsense mutation in exon 4 and a heterozygous missense mutation in exon 8. The nonsense mutation in exon 4, which caused a change from CGA to TGA at position 144 and resulted in the substitution of arginine by termination codon（p.R144*）, was a novel mutation in the BCS1L gene causing Bj-rnstad syndrome, and had never been reported in the literature. The missense mutation in exon 8 led to a change from CGC to CAC at position 306 and resulted in the substitution of arginine by histidine （p.R306H）. The patient′s mother only carried a heterozygous mutation c.430 C>T （p.R144*） in exon 4 of the BCS1L gene, and her father only carried a heterozygous mutation c.917 G>A （p.R306H） in exon 8 of the BCS1L gene. Scanning electron microscopy showed that flats, grooves and longitudinal twisting irregularly appeared at intervals on the surface of hair shafts. Conclusions A novel mutation in the BCS1L gene, which causes a change from CGA to TGA at position 144 in the BCS1L gene and results in a premature termination codon, is firstly reported in a patient with Bj-rnstad syndrome, and the compound heterozygous mutations c.430 C>T and c.917 G>A in the BCS1L gene are associated with the clinical manifestations of the patient. Genetic analysis is helpful for the diagnosis of Bj-rnstad syndrome.

Key words: Mitochondrial diseases, Genes, mitochondrial, DNA mutational analysis, Bj-rnstad syndrome, BCS1L gene

引用本文

李思源 刘婷婷 杨淑霞 马圣清 杨勇. Bjornstad综合征致病BCS1L基因的新发突变位点研究[J]. 中华皮肤科杂志, 2020,53(2):93-97. doi:10.35541/cjd.20190740

Li Siyuan, Liu Tingting, Yang Shuxia, Ma Shengqing, Yang Yong. Identification of a novel mutation in the BCS1L gene causing Bjornstad syndrome[J]. Chinese Journal of Dermatology, 2020, 53(2): 93-97.doi:10.35541/cjd.20190740