Abstract:

Objective: To report 2 cases of Charcot-Marie-Tooth disease type 4H (CMT4H) caused by FGD4 gene variation and review the relevant literatures, summarizing the clinical and gene mutation characteristics of CMT4H. Methods and Results: Two families with CMT4H diagnosed by genetic test in Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine from May 2020 to July 2022 were included. The probands in 2 families were both sporadic patients with onset in early adolescence, manifesting as progressive postural gait abnormalities, difficulty walking, and foot deformities. Nerve electrophysiological examination showed multiple demyelinating damages to sensory and motor nerves. Sural nerve biopsy in proband of family 1 disclosed a decreased density of myelin fibers and demyelinating neuropathy with thickened and excessively folded myelin sheath. Whole exome sequencing (WES) revealed that both probands had compound heterozygous mutations in the FGD4 gene, all of which were novel, and cosegregated with the family members. Conclusions: CMT4H is a peripheral neuropathy mainly caused by autosomal recessive demyelination, and case report from 2 families further expand the spectrum of FGD4 gene mutations.

Key words: Charcot-Marie-Tooth disease, Peripheral nervous system diseases, Genes, Mutation, Pedigree

摘要：

目的: 报道2例FGD4基因变异致腓骨肌萎缩症4H型（CMT4H型）患儿，并复习相关文献，总结CMT4H型的临床和基因突变特点。方法与结果: 纳入2020年5月至2022年7月在上海交通大学医学院附属第六人民医院经基因检测确诊的2例CMT4H型患儿，均为散发病例，青春期早期发病，表现为进行性姿势、步态异常，行走困难和足部畸形；电生理检测均提示四肢多发感觉和运动神经损害，以脱髓鞘改变为主。家系1先证者腓肠神经组织活检显示有髓纤维密度减少、薄髓鞘纤维及个别髓鞘异常折叠或增厚。全外显子组测序显示，家系1先证者存在FGD4基因c.1688C > A（p.Thr563Lys）和c.1951C > T（p.Gln651Ter）复合杂合突变，家系2先证者存在FGD4基因c.694T > C（p.Phe232Leu）和c.1673G > A（p.Arg558Gln）复合杂合突变，均为新发突变，且符合家系共分离特点。结论: CMT4H型为常染色体隐性遗传性脱髓鞘型周围神经系统疾病，两家系报道进一步扩宽FGD4基因突变谱。

关键词: 夏科-马里-图斯病, 周围神经系统疾病, 基因, 突变, 系谱