腓骨肌萎缩症伴神经性耳聋一家系临床和分子遗传学分析

<title>inical features and molecular genetic analysis of a Charcot-Marie-Tooth disease family with sensorineural deafness

目的探讨一个X连锁腓骨肌萎缩症(CMTX)伴常染色体隐性遗传的神经性耳聋家系的临床特点并研究其分子遗传学病因。方法对9名家系成员进行详细的临床检查,先证者进行了神经肌电图、听觉诱发电位和神经活检,3名耳聋患者进行电测听检查。运用聚合酶链反应-单链构象多态性分析技术(PCR-SSCP)结合直接测序法进行间隙连接蛋白32(connexin32)的突变分析,直接测序法进行间隙连接蛋白26(connexin26)的突变分析。结果家系中3名腓骨肌萎缩症患者为X连锁显性遗传,3名神经性耳聋患者为常染色体隐性遗传,其中1名患者同时出现腓骨肌萎缩症和神经性耳聋的临床症状。CMTX由connexin32错义突变C223T(Arg75Trp)引起。耳聋症状与connexin32点突变无共分离现象,对connexin26直接测序亦未发现突变,耳聋的致病基因有待进一步探讨。结论该家系腓骨肌萎缩症和耳聋分别由不同基因突变引起,这种在一个家系中同时出现两种不同遗传方式,不同致病基因的遗传病罕有报道。

<abstract>jective To investigate the clinical features and gene mutations of a Charcot-Marie-Tooth disease family with sensorineural deafness. Methods Nine family members underwent detailed clinical examinations. The proband received electromyography, nerve conduction study, brainstem auditory evoked potentials and nerve biopsy. Audiometric testing was performed in the three deaf patients. CX32 mutation analysis was screened by the use of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) combined with direct sequencing in nine family members. Direct sequencing was used to screen the CX26 mutation. Results There were three CMTX patients and three autosomal recessive nonsyndromic hearing loss patients in the family, with one patient having both CMT symptoms and hearing loss. The CX32 missence mutation C223T (Arg75Trp) was accounted for the CMT phenotype but not for sensorineural deafness. CX26 was not the causal gene for sensorineural deafness either. Further mutation analysis for sensorineural deafness was to be performed. Conclusion The hearing loss symptom was one of the distinct features in the previous reported CMT family. While in this family we reported, different gene mutations should be accounted for the CMT and hearing loss respectively. It was rare that two causal genes were mutated by different hereditary traits in one family.