摘要：

目的 探讨腓骨肌萎缩症4B2 型（CMT4B2 型）的临床表型和分子遗传学特征。方法 一家系3 例CMT4B2 型患儿，采用目标区域捕获测序技术检测MTMR13/SBF2 基因突变类型。结果 例1（先证者）6 年前出现双下肢无力，行走向前跨步，跑步速度较同班同学明显缓慢，随后症状逐渐加重，出现双手大小鱼际肌和骨间肌萎缩，双侧指关节不能伸直，双侧小腿肌萎缩，双侧马蹄内翻足和四肢腱反射减弱。例2（先证者之大弟）2 年前出现双下肢无力，行走不稳，跑步和上楼梯较前明显缓慢，步态异常逐渐加重，足跟行走不能，双手大小鱼际肌萎缩，双侧小腿轻度肌萎缩，四肢腱反射减弱。例3（先证者之二弟）足跟行走困难，双手大小鱼际肌轻度肌萎缩，四肢腱反射减弱。基因检测显示，例1 存在MTMR13/SBF2 基因c.230G > A（p.Gln77Arg）和c.1537C > T（p.Gln513*）复合杂合突变，其父携带c.230G >A（p.Gln77Arg）杂合突变，其母携带c.1537C > T（p.Gln513*）杂合突变，例2 和例3 均存在与先证者相同的c.230G > A（p.Gln77Arg）和c.1537C > T（p.Gln513*）复合杂合突变。3 例患儿诊断明确为CMT4B2 型，该家系明确诊断为CMT4B2 型家系。予甲钴胺对症治疗，先证者马蹄内翻足明显，予石膏固定疗法予以纠正。结论 CMT4B2 型是罕见且严重的进展型腓骨肌萎缩症，目前尚无有效治疗方法，对患者进行及时的基因检测以明确诊断，同时对患病家系积极开展遗传咨询，对于有生育要求的致病基因携带者还应结合产前基因诊以避免患病胎儿的出生。对于家系中携带致病基因尚未出现临床症状或处于疾病早期的患者，应密切随访，采取积极治疗以尽可能延迟发病时间或指导患者进行正确的康复训练以预防弓形足、脊柱侧弯等畸形，从而提高生活质量。

关键词: 夏科-马里-图斯病, 表型, 基因, 突变, 系谱

Abstract:

Objective To explore the clinical features and genetic characteristics of Charcot-Marie-Tooth disease type 4B2 (CMT4B2) patients. Methods MTMR13/SBF2 gene mutations were screened by target region capture sequencing among a CMT4B2 Chinese family which included 3 patients. Results Case 1 (the proband) showed weakness in both lower limbs 6 years ago, running significantly slower than her classmates. The symptoms then became gradually worsened. Then the patient suffered from amyotrophy of thenar and hypothenar eminences and interosseus of her hands, bilateral finger joints could not be straightened, atrophy of bilateral leg muscles, talipes equinovarus appearance, and weakened tendon reflexes of limbs. Case 2 (the proband's younger brother) had weakness in both lower limbs and walked unsteadily 2 years ago, with running and going upstairs significantly slower than before. His abnormal walking gait got worsening in recent and he could not bend his feet upward in the stand or on the walk. He also presented amyotrophy of thenar and hypothenar eminences of his hands, mild atrophy of bilateral leg muscles, talipes equinovarus appearance, and weakened tendon reflex of limbs. Case 3 (the proband's another younger brother) also had difficulty in walking with the heel, and thenar and hypothenar eminences of his hands were mildly atrophic and the tendon reflexes were weakened. The result of proband's MTMR13/SBF2 gene test showed c.230G > A (p.Gln77Arg) and c.1537C > T (p.Gln513*) compound heterozygous mutations, her father carried c.230G > A (p.Gln77Arg) heterozygous mutation and her mother carried c.1537C > T (p.Gln513*) heterozygous mutation. Case 2 and Case 3 had the same compund heterozygous mutation as the proband. The 3 patients were diagnosed as CMT4B2, and their family was diagnosed as CMT4B2 pedigree. All patients were treated by mecobalamine. The proband was also treated by plaster immobilization to correct her talipes equinovarus. Conclusions CMT4B2 is a very rare and serious progressive type of CMT. Since there is no effective treatment of CMT4B2, we should carry out gene test as early as possible to make a clear diagnosis on patients and also take hereditary inquiry on the patient's family. For disease-causing gene carriers who want to have a baby, prenatal genetic diagnosis should be done to avoid the birth of CMT4B2 baby. For carriers of the gene without clinical symptoms or in early stage, close follow-up and active treatment should be taken to delay the onset and prevent talipes equinovarus or scoliosis, so as to improve the life quality of patients.

Key words: Charcot-Marie-Tooth disease, Phenotype, Genes, Mutation, Pedigree