腓骨肌萎缩症2个家系的临床、电生理和基因学研究

Clinical,electrophysiological,and genetic studies of two families with Charcot-Marie-Tooth disease

为了研究腓骨肌萎缩症(CMT)的临床、电生理以及基因突变的特点,该研究收集2个家系先证者以及发病亲属的临床资料、电生理资料、全血和DNA,进行家系分析及CMT相关基因检测。结果发现家系1为常染色体显性遗传,患者MLPA检测提示PMP22基因的重复扩增。基因测序未发现患者携带CMT其他相关基因的突变。进一步在患者的3个患病的亲属中发现携带PMP22基因的重复扩增,并且未发现其未患病的叔叔携带该突变。家系2为常染色体隐性遗传,先证者携带SH3TC2基因的c.730C>Tp.Q244X和c.432C>Gp.Y144X两个杂合突变。患者的父母,则分别携带上述两个突变。因此,家系1诊断为CMT1A型,家系2诊断为CMT4C型,临床实践中应注意基因和表型的联系。

In order to investigate the clinical,electrophysiological,and genetic features of two families with Charcot-Marie-Tooth disease(CMT),this study collected the clinical data,electrophysiological data,whole blood,and DNA of the probands and their relatives in the two families,and the pedigree analysis and CMT-related gene detection were performed.Family 1 was found to have autosomal dominant inheritance,and MLPA test of the proband showed repeated amplification of the PMP22 gene;gene sequencing did not reveal mutations in other CMT-related genes;further detection found repeated amplification of the PMP22 gene in three relatives of the proband,which was not found in the uncles without the disease.Family 2 was found to have autosomal recessive inheritance;the proband carried two heterozygous mutations of the SH3TC2 gene,i.e.,c.730C>T p.Q244X and c.432C>G p.Y144X,and each of the proband’s parents carried one of the two mutations. Therefore,Family 1 was diagnosed with CMT1A and Family 2 was diagnosed with CMT4C. The association between gene and phenotype should be taken seriously in clinical practice.