Whole exome sequencing reveals a broader variant spectrum of Charcot-Marie-Tooth disease type 2
Whole exome sequencing reveals a broader variant spectrum of Charcot-Marie-Tooth disease type 2
复制标题
全外显子组测序揭示了 2 型腓骨肌萎缩症更广泛的变异谱
DOI：
10.1007/s10048-019-00591-4
复制
发表时间：
2020-04-01
期刊：
影响因子：
2.2
通讯作者：
He, Jin
中科院分区：
文献类型：
--
作者：
Lin, Shan;Xu, Liu-Qing;He, Jin
Charcot-Marie-Tooth病2型（CMT2）是一种临床和遗传异质性的遗传性神经病变。尽管近年来已经发现了CMT2的新的致病基因和疾病相关基因，但大多数患者仍然缺乏分子诊断。我们在此研究了35名华裔CMT2患者，使用全外显子组测序研究基因突变，然后通过液滴数字PCR评估基因型，临床特征和血液中线粒体DNA水平之间的关系。我们在57%的CMT2患者中发现了致病变异。该队列中最常见的遗传原因是MFN2突变。两例具有典型CMT表型和神经肌强直的患者检测到HINT1基因的复合杂合变异。总之，我们的工作支持通过全外显子组测序可以提高CMT2患者的分子诊断率，我们的数据表明，对于神经肌强直的CMT2患者，应该对可能的HINT1突变进行评估。
Charcot-Marie-Tooth disease type 2 (CMT2) is a clinically and genetically heterogeneous inherited neuropathy. Although new causative and disease-associated genes have been identified for CMT2 in recent years, molecular diagnoses are still lacking for a majority of patients. We here studied a cohort of 35 CMT2 patients of Chinese descent, using whole exome sequencing to investigate gene mutations and then explored relationships among genotypes, clinical features, and mitochondrial DNA levels in blood as assessed by droplet digital PCR. We identified pathogenic variants in 57% of CMT2 patients. The most common genetic causes in the cohort were MFN2 mutations. Two patients with typical CMT phenotype and neuromyotonia were detected to harbor compound heterozygous variations in the HINT1 gene. In conclusion, our work supports that the molecular diagnostic rate of CMT2 patients can be increased via whole exome sequencing, and our data suggest that assessment of possible HINT1 mutations should be undertaken for CMT2 patients with neuromyotonia.