Mutation screening of PDGFB gene in Chinese population with primary familial brain calcification
Mutation screening of PDGFB gene in Chinese population with primary familial brain calcification
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中国原发性家族性脑钙化人群PDGFB基因突变筛查
DOI：
10.1016/j.gene.2016.10.037
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发表时间：
2017
期刊：
影响因子：
3.5
通讯作者：
Chen Wan-Jin
中科院分区：
文献类型：
--
作者：
Yao Xiang -Ping;Wang Chong;Su Hui-Zhen;Guo Xin-Xin;Lu Ying-Qian;Zhao Miao;Liu Yao-Bin;Lai Jing-Hui;Chen Hai-Ting;Wang Ning;Chen Wan-Jin
背景原发性家族性脑钙化（PFBC）是由4个基因决定的，分别是SLC 20 A2、PDGFRB、PDGFB和XPR 1。目的在中国人群中筛查无SLC 20 A2突变的原发性肺纤维化（PFBC）患者的PDGFB基因突变。采集所有入选受试者的外周静脉血样本用于基因组DNA提取。采用聚合酶链反应（PCR）扩增PDGFBs基因编码序列，并进行序列测定。通过生物信息学分析评估了所确定的变异体对蛋白质功能的潜在影响。结果在5例散发性PFBC患者中发现了3种错义变异体（c.35G > T、c.232C > T和c.610C > A）和1种无义变异体（c.220G > T）。在2名来自同一种族背景的健康对照中发现了变异c.35G > T，而在500名对照中没有发现c.220G > T、c.232C > T和c.610C > A。c.220G > T（p.E74*）在谷氨酸残基编号74处产生终止密码子。c.232C > T（p.R78C）发生在高度保守的区域，并且被至少两个计算预测程序预测为破坏性的，这表明该变体可能在PFBC中具有因果作用。虽然变异c.610C > A（p.P204T）也发生在一个高度保守的区域，它被预测为最有可能是良性的两个计算预测程序，这表明一个不确定的作用PFBC.ConclusionsThe本研究确定了一个可能的致病变异（p.E74*）和两个变异的不确定意义（p.R78C和p.P204T）在PDGFB。这些变异体的PDGF-B功能表达的进一步研究仍需要确认致病作用。
BackgroundUntil recently, primary familial brain calcification (PFBC) has been determined by four genes,SLC20A2, PDGFRB, PDGFB and XPR1. No studies have been carried out to analyze the gene mutation ofPDGFBin Chinese population.ObjectiveTo screen mutations ofPDGFBgene in a large cohort of Chinese PFBC patients with noSLC20A2mutations.MethodsWe recruited 192 PFBC patients, including 21 index cases and 171 sporadic cases, in our study. Peripheral venous blood samples of all included participants were collected for genomic DNA extraction. The coding sequence ofPDGFBwas amplified by polymerase chain reaction (PCR) followed by direct sequencing. The potential effects of the identified variants on protein function were assessed by bioinformatics analysis.ResultsThree missense variants (c.35G > T, c.232C > T, and c.610C > A) and one nonsense variant (c.220G > T) ofPDGFBwere identified in five sporadic PFBC patients. The variant c.35G > T was found in 2 healthy controls from the same ethnic background, whereas c.220G > T, c.232C > T and c.610C > A were absent from 500 controls. c.220G > T (p.E74*) produced a stop codon in the place of the glutamic acid residue number 74. c.232C > T (p.R78C) occurred at highly conserved regions and were predicted as damaging by at least two computational predictive programs, suggesting that this variant was likely to have a causal role in PFBC. Although variant c.610C > A (p.P204T) also occurred at a highly conserved region, it was predicted to be most likely benign by two computational predictive programs, suggesting an uncertain role of this variant on PFBC.ConclusionsThe present study identified one likely pathogenic variant (p.E74*) and two variants of uncertain significance (p.R78C and p.P204T) inPDGFB. Further studies of PDGF-B functional expression for these variants are still required to confirm the pathogenic effect.