线粒体融合蛋白2基因突变致夏科-马里-图斯病2A2亚型的表型分析

Analysis of the clinical phenotypes of Charcot -Marie -Tooth disease type 2A2 patients with mitofusin2 mutation

目的 探讨夏科-马里-图斯病2型（CMT2）患者线粒体融合蛋白（MFN2）基因突变特征及临床变异性.方法 收集临床拟诊的8个常染色体显性遗传CMT2家系和24个散发CMT2病例,采用PCR技术和直接测序方法进行MFN2基因突变检测,详细分析阳性病例的临床表型.结果 在32例拟诊CMT2病例中共检测出4种MFN2基因的错义突变,检出率为12.5%.其中c.281G＞A（R94Q）和c.2240 T＞C（M747T）分别见于2个常染色体显性遗传家系,同一家系内部存在表型差异;c.1090 C＞T（R364W）和c.2198 T＞C（L733P）分别见于2例散发病例,后者为首次报道的新突变,除四肢远端萎缩无力外,前者伴视神经萎缩,后者伴皮肤过度角化.结论 MFN2基因突变为中国人群CMT2型常见病因,通过分析CMT2A2患者的临床表型,提示该组疾病具有高度的临床变异性.

Objective To investigate the characteristics of mitofusin2 （MFN2） mutation and the clinical variability of Charcot-Marie-Tooth disease type 2 （ CMT2 ） patients. Methods MFN2 mutation analysis were performed in 8 autosomal dominant CMT2 families and 24 sporadic CMT2 cases by PCR and direct sequencing. The clinical features of the positive cases were precisely analyzed. Results Sequencing of the MFN2 gene revealed 4 different missense mutations, and detection rate was 4 of 32 （ 12. 5% ） in patients with CMT2. c. 281G 〉 A （R94Q） and c. 2240 T 〉 C （M747T）were detected in 2 autosomal dominant pedigrees, and intrafamilial clinical phenotype variability was present;c. 1090 C 〉 T （R364W）and c. 2198 T 〉 C （L733P） were detected in 2 sporadic cases ,and the latter was a novel mutation which had not been reported. In addition to weakness and atrophy in the distal limbs, the former sporadic case was optic atrophy, and the latter case was hyperkeratosis of the skin. Conclusions Divergent MFN2 mutations are frequently found among axonal varieties of CMT2 in the Chinese population, and analysis of phenotypes in the CMT2A2 patients indicate the high clinical variability of this disease.