中国人山梨醇脱氢酶基因相关腓骨肌萎缩症的基因型-表型分析  

Genetic and clinical features of sorbitol dehydrogenase gene-related Charcot-Marie-Tooth disease in Chinese population

作　　者：林志强 李小波[1] 黄顺祥[1] 赵华栋[1] 刘蕾[1] 曹婉芊 刘鑫 唐北沙[2] 张如旭[1] Lin Zhiqiang;Li Xiaobo;Huang Shunxiang;Zhao Huadong;Liu Lei;Cao Wanqian;Liu Xin;Tang Beisha;Zhang Ruxu(Department of Neurology,the Third Xiangya Hospital of Central South University,Changsha 410013,China;Department of Neurology,Xiangya Hospital of Central South University,Changsha 410008,China)

机构地区：[1]中南大学湘雅三医院神经内科,长沙410013 [2]中南大学湘雅医院神经内科,长沙410008

出　　处：《中华神经科杂志》2020年第11期882-887,共6页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目(81771366);湖南省卫生计生委科研计划课题(A2017001);湖南省自然科学基金重点资助项目(2017JJ2365);中华国际医学基金会资助项目(CIMF-Z-2016-20-1801)。

摘　　要：目的报道中国人群中山梨醇脱氢酶(SORD)基因相关腓骨肌萎缩症(CMT)的基因型和表型特点。方法从2009—2018年在中南大学湘雅三医院收集的CMT患者中选择57个未明确基因诊断的、散发或常染色体隐性遗传(AR)的轴索型CMT(CMT2)家系。应用聚合酶链反应(PCR)结合Sanger测序法进行SORD基因的突变检测,并总结SORD基因相关CMT患者的表型特点。结果在4例无家族史患者中检测到SORD基因纯合c.757delG(p.Ala253GlnfsTer27)突变,约占该组患者总数的7%。2例患者表现为慢性进行性双下肢肌无力和肌萎缩、运动和感觉神经轴索变性电生理改变的CMT2;另2例患者表现为慢性进行性双下肢肌无力和肌萎缩,仅运动神经轴索变性电生理改变的遗传性远端运动神经病(dHMN)。患者发病年龄为5~16岁,CMT神经病变评分为2~9分。结论首次在中国CMT患者中报道SORD基因纯合热点突变c.757delG(p.Ala253GlnfsTer27)及其对应的儿童/青少年期起病、神经功能轻度受损的CMT2和dHMN表型。SORD基因相关CMT可能是最常见的AR-CMT2基因亚型。Objective To report the genetic and clinical features of sorbitol dehydrogenase(SORD)gene-related Charcot-Marie-Tooth disease(CMT)in Chinese population.Methods Fifty-seven undiagnosed sporadic or autosomal recessive(AR)inherited CMT2 families were collected from the Department of Neurology of the Third Xiangya Hospital from 2009 through 2018.Polymerase chain reaction combined with Sanger sequencing were used to detect the mutations of SORD gene,and the relative clinical features were summarized.Results The homozygous SORD gene hot spot mutation c.757delG(p.Ala253GlnfsTer27)was detected in four sporadic patients,accounting for about 7%of the total.Two patients with CMT2 phenotype were characterized by progressive lower limb weakness and atrophy with electromyogram changes of axonal degeneration in both motor and sensory nerves.Two patients with distal hereditary motor neuropathy(dHMN)phenotype exhibited progressive lower limb weakness and atrophy with electromyogram changes of axonal degeneration in motor nerves only.The age of onset was between five and 16 years,and the CMT neuropathy score was 2-9.Conclusions The homozygous hot spot mutation of SORD gene(c.757delG,p.Ala253GlnfsTer27),and related childhood or adolescence onset,mildly affected CMT2/dHMN phenotypes are firstly reported in Chinese population.SORD gene-related CMT might be the most common subtype of AR-CMT2.

关 键 词：山梨醇脱氢酶基因 常染色体隐性遗传 轴索型腓骨肌萎缩症 遗传性远端运动神经病 

分 类 号：R746.4[医药卫生—神经病学与精神病学]