TFG基因c.854 C>T突变的HMSN-P家系临床特征及文献复习

Clinical characteristics of HMSN-P families with TFG gene(c.854C>T)mutation and related literature review

目的通过收集一个罕见的近端优势型遗传性运动感觉神经病(HMSN-P)家系的患者临床资料,结合原肌球蛋白受体激酶融合基因(TFG)突变位点对其临床特征进行分析总结。方法收集在徐州医科大学附属医院首诊的HMSN-P家系先证者及其家系共4代13例成员(包括患者8例)的临床资料,抽取其中10例的外周血提取DNA进行高通量测序及Sanger测序。结果先证者成年起病,进展加重的四肢近端肌无力萎缩,伴有显著的痛性肌肉痉挛和肌束震颤,早期肌电图提示脊髓前角受累,高度提示运动神经元病。家系中的其他患者与先证者症状相似,部分患者血清肌酸激酶(CK)明显升高。经测序患者均存在TFG基因c.854C>T杂合突变,该突变与疾病表型存在共分离,且该位点为HMSN-P已知的致病性突变位点。结论早期脊髓前角细胞受累导致的近端肌无力萎缩是TFG基因c.854C>T杂合突变的HMSN-P患者的显著临床特征,部分患者可合并肌肉受累。

Objective To collect the clinical data of a rare hereditary motor and sensory neuropathy with proximal predominance(HMSN-P)family and summarize the clinical characteristics based on TFG gene mutation.Methods The clinical data of 13 members of 4 generations(including 8 patients)who were originally diagnosed proband in the Affiliated Hospital of Xuzhou Medical University and their families were collected.DNA samples were collected from the peripheral blood of 10 members for high throughput sequencing and Sanger sequencing.Results The adult-onset proband presented progressive weakness and atrophy of the proximal muscles of the extremities,accompanied by significant painful muscle spasms and muscle bundle tremors.Early electromyography suggested the involvement of the anterior horn of the spinal cord,and motor neuron disease was highly suggested.Other patients in the family showed similar symptoms to the proband,and some had significantly elevated levels of serum creatine kinase(CK).After sequencing,the TFG gene c.854C>T heterozygous mutation was detected in all patients,and co-segregated with the disease phenotype,which was a known pathogenic mutation of HMSN-P.Conclusions Early weakness and atrophy of the proximal muscle with involvement of spinal anterior cells is a significant clinical feature of HMSN-P patients with TFG gene c.854C>T heterozygous mutation,and muscle problems may accompany with in some patients.