Li Qian, Zhang Yongpeng, Jia Liyun, Peng Xiaoyan
Beijing Tongren Eye Center, Beijing Key Laboratory of Ophthalmology and Visual Science, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
Beijing Tongren Eye Center, Beijing Key Laboratory of Ophthalmology and Visual Science, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; Beijing Institute of Ophthalmology, Beijing Key Laboratory of Ophthalmology and Visual Science, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
Chin Med J (Engl). 2014;127(24):4190-6.
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disease, and information about BBS in Chinese populations is very limited. The purpose of the present study was to determine the genetic cause of BBS in a Chinese Han family.
Clinical data were recorded for the 4-year-old female proband and the available family members. The proband was screened for mutation by Sanger sequencing for a total of 142 exons of the 12 BBS-causing genes (BBS1-BBS12). The variants detected in the proband were further confirmed in the other family members.
We identified a novel homozygous nonsense mutation (c.70A>T, p.K24X) in the BBS4 gene exon 2 in the proband. Such mutant allele was predicted to cause a premature truncation in the N-terminal of the BBS4 protein, and probably induced the nonsense-mediated decay of BBS4 messenger RNAs. The proband's parents and brother were heterozygous for the nonsense mutant allele. It was absent in 50 Chinese control subjects. An additional rare heterozygous missense single nucleotide polymorphism (SNP) named rs200718870 in BBS10 gene was also detected in the proband, her father and her brother. Some manifestations of the proband including atypical retinitis pigmentosa, choroidal sclerosis, high myopia, and early onset of obesity might be associated with this mutation in BBS4 gene. The proband's father also reported surgical removal of an extra finger during childhood.
The present study described a novel nonsense mutation in BBS4 gene in a Chinese family. This homozygous mutation was predicted to completely abolish the synthesis of the BBS4 protein. We also detected a rare heterozygous missense SNP in BBS10 gene in the family, but did not find sufficient evidence to support the triallelic inheritance.
巴德-比埃尔综合征（BBS）是一种基因异质性疾病，关于中国人群中BBS的信息非常有限。本研究的目的是确定一个中国汉族家庭中BBS的遗传病因。
记录了4岁女性先证者及其他可用家庭成员的临床数据。通过桑格测序对12个导致BBS的基因（BBS1 - BBS12）的总共142个外显子进行先证者突变筛查。在先证者中检测到的变异在其他家庭成员中进一步确认。
我们在先证者的BBS4基因外显子2中鉴定出一个新的纯合无义突变（c.70A>T，p.K24X）。这种突变等位基因预计会导致BBS4蛋白N端的过早截断，并可能诱导BBS4信使核糖核酸的无义介导衰变。先证者的父母和兄弟为该无义突变等位基因的杂合子。在50名中国对照受试者中未发现该突变。在先证者、其父亲和其兄弟中还检测到BBS10基因中一个额外的罕见杂合错义单核苷酸多态性（SNP），名为rs200718870。先证者的一些表现，包括非典型色素性视网膜炎、脉络膜硬化、高度近视和肥胖早发，可能与BBS4基因的这种突变有关。先证者的父亲还报告在童年时期接受过多指切除手术。
本研究描述了一个中国家庭中BBS4基因的新无义突变。这种纯合突变预计会完全消除BBS4蛋白的合成。我们还在该家庭中检测到BBS10基因中的一个罕见杂合错义SNP，但没有找到足够的证据支持三基因座遗传。
