Screening for SH3TC2, PMP2, and BSCL2 Variants in a Cohort of Chinese Patients with Charcot-Marie-Tooth.
Screening for SH3TC2, PMP2, and BSCL2 Variants in a Cohort of Chinese Patients with Charcot-Marie-Tooth.
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在中国腓骨肌萎缩症患者队列中筛查 SH3TC2、PMP2 和 BSCL2 变异
DOI：
10.4103/0366-6999.222331
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发表时间：
2018-01-20
影响因子：
6.1
通讯作者：
Zhang RX
中科院分区：
文献类型：
--
作者：
Zhao X;Jiang MM;Yan YZ;Liu L;Xie YZ;Li XB;Hu ZM;Zi XH;Xia K;Tang BS;Zhang RX
工作背景：SH 3 TC 2、PMP 2和BSCL 2基因分别与常染色体隐性（AR）Charcot-Marie-Tooth（CMT）疾病1型、常染色体显性（AD）-CMT 1和AD-CMT 2相关。这三个基因的致病性变异在中国CMT患者中没有很好的记录。因此，本研究旨在检测315个无关的中国CMT家族中的SH 3 TC 2、PMP 2和BSCL 2致病性变异。研究方法：从湘雅三医院神经内科和湘雅医院神经内科共收集315个CMT家系的315名先证者。我们使用聚合酶链反应和桑格测序，在84例AR或散发性CMT先证者中筛查SH 3 TC 2致病性变异，在39例AD或散发性CMT 1先证者中筛查PMP 2致病性变异，在50例AD或散发性CMT 2先证者中筛查BSCL 2致病性变异。所有这些患者均来自315个不相关的中国CMT家系，在排除致病性PMP 22、MFN 2、MPZ、GJB 1、GDAP 1、HSPB 1、HSPB 8、EGR 2、NEFL和RAB 7的致病性变体后，未被诊断。根据美国医学遗传学和基因组学学院（ACMG）的标准和指南对候选变异体进行分析。重新评估了临床特征。结果如下：我们鉴定了SH 3 TC 2基因的三种新的杂合变体，如p.L95V（c.283C>G）、p.L1048P（c.3143T>C）和p.V1105M（c.3313G>A），而没有发现PMP 2和BSCL 2基因的致病变体。尽管在健康对照中的计算机模拟评估和筛选显示三种SH 3 TC 2变体可能是致病性的，但未发现第二等位基因变体。根据ACMG的标准和指南，p.L95V、p.L1048P和p.V1105M等杂合SH 3 TC 2变异体被认为意义不确定。结论：中国CMT患者中SH 3 TC 2、PMP 2和BSCL 2致病性变异可能是罕见的。需要进一步的研究来证实我们的发现。
Background: SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive (AR) Charcot-Marie-Tooth (CMT) disease type 1, autosomal dominant (AD)-CMT1, and AD-CMT2, respectively. Pathogenic variants in these three genes were not well documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2, PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT families. Methods: A total of 315 probands from 315 unrelated Chinese CMT families were recruited from the Department of Neurology of Third Xiangya Hospital and Xiangya Hospital. We screened for SH3TC2 pathogenic variants in 84 AR or sporadic CMT probands, PMP2 pathogenic variants in 39 AD or sporadic CMT1 probands, and BSCL2 pathogenic variants in 50 AD or sporadic CMT2 probands, using polymerase chain reaction and Sanger sequencing. All these patients were out of 315 unrelated Chinese CMT families and genetically undiagnosed after exclusion of pathogenic variants of PMP22, MFN2, MPZ, GJB1, GDAP1, HSPB1, HSPB8, EGR2, NEFL, and RAB7. Candidate variants were analyzed based on the standards and guidelines of American College of Medical Genetics and Genomics (ACMG). Clinical features were reevaluated. Results: We identified three novel heterozygous variants such as p.L95V (c.283C>G), p.L1048P (c.3143T>C), and p.V1105M (c.3313G>A) of SH3TC2 gene and no pathogenic variants of PMP2 and BSCL2 genes. Although evaluation in silico and screening in the healthy control revealed that the three SH3TC2 variants were likely pathogenic, no second allele variants were discovered. According to the standards and guidelines of ACMG, the heterozygous SH3TC2 variants such as p.L95V, p.L1048P, and p.V1105M were considered to be of uncertain significance. Conclusions: SH3TC2, PMP2, and BSCL2 pathogenic variants might be rare in Chinese CMT patients. Further studies to confirm our findings are needed.
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