2F 型腓骨肌萎缩症与 HSPB1 双等位基因突变相关。
Charcot-Marie-Tooth disease type 2F associated with biallelic HSPB1 mutations.
机构信息
Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, University of Milan, Milan, Italy.
Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
出版信息
Ann Clin Transl Neurol. 2021 May;8(5):1158-1164. doi: 10.1002/acn3.51364. Epub 2021 May 4.
OBJECTIVE
This work aims to expand knowledge regarding the genetic spectrum of HSPB1-related diseases. HSPB1 is a gene encoding heat shock protein 27, and mutations in HSPB1 have been identified as the cause of axonal Charcot-Marie-Tooth (CMT) disease type 2F and distal hereditary motor neuropathy (dHMN).
METHODS
Two patients with axonal sensorimotor neuropathy underwent detailed clinical examinations, neurophysiological studies, and next-generation sequencing with subsequent bioinformatic prioritization of genetic variants and in silico analysis of the likely causal mutation.
RESULTS
The HSPB1 p.S135F and p.R136L mutations were identified in homozygosis in the two affected individuals. Both mutations affect the highly conserved alpha-crystallin domain and have been previously described as the cause of severe CMT2F/dHMN, showing a strictly dominant inheritance pattern.
INTERPRETATION
Thus, we report for the first time two cases of biallelic HSPB1 p.S135F and p.R136L mutations in two families.
目的
本研究旨在扩展 HSPB1 相关疾病的遗传谱知识。HSPB1 是一种编码热休克蛋白 27 的基因，HSPB1 突变已被确定为轴索性夏科-马里-图病（CMT）2F 型和遗传性运动神经病（dHMN）的病因。
方法
两名患有轴索性感觉运动神经病的患者接受了详细的临床检查、神经生理学研究以及下一代测序，随后对遗传变异进行了生物信息学优先级排序，并对可能的致病突变进行了计算机分析。
结果
在两名受影响的个体中均发现 HSPB1 p.S135F 和 p.R136L 突变呈纯合状态。这两种突变均影响高度保守的α-晶状体蛋白结构域，并且以前曾被描述为严重 CMT2F/dHMN 的病因，表现为严格的显性遗传模式。
结论
因此，我们首次在两个家族中报告了 HSPB1 p.S135F 和 p.R136L 双等位基因突变的两个病例。
Zotero 插件