夏科-马里-图思病Cx32、MPZ和PMP22基因点突变的特点

Point mutation of Cx32, MPZ and PMP22 genes in Chinese CharcotMarieTooth disease

目的研究我国夏科马里图思病（ＣＭＴ）Ｃｘ３２、ＭＰＺ和ＰＭＰ２２基因点突变的特点。方法应用聚合酶链反应单链构象多态性（ＰＣＲＳＳＣＰ）结合ＤＮＡ序列分析检测３０个ＣＭＴ家系的患者及５０名非血缘关系的正常对照的Ｃｘ３２、ＭＰＺ和ＰＭＰ２２基因的编码外显子。结果４个家系（３个为Ｘ连锁隐性遗传）有４种不同的Ｃｘ３２基因点突变（１３．３％），其中１个家系为１８８位的苏氨酸被丙氨酸置换是未见报道的新突变。１个家系（３．３％）有ＭＰＺ基因点突变，未发现ＰＭＰ２２基因的点突变。结论Ｃｘ３２、ＭＰＺ和ＰＭＰ２２基因的点突变占ＣＭＴ致病原因的１６．７％。我国也存在不少Ｘ连锁遗传的家系（＞１０．０％），对可疑的家系（家系中患者无男传男的现象）应首先进行Ｃｘ３２基因的点突变检测。我国的ＣＭＴ发病率低可能与其基因突变特点有关。

Objective To study the characteristics of the point mutations of Cx32, MPZ and PMP22 genes in Chinese CharcotMarieTooth disease(CMT). Methods The coding exons of Cx32, MPZ and PMP22 genes were screened in 30 families of Chinese CMT and 50 unrelated normal persons by polymerase chain reactionsingle strand conformation polymorphism. Results Four (13.3%) different point mutations (3 had been described previously) were found in 4 families (3 with Xlinkage ressesive transmission). One of the point mutations, Thr188Ala ,which was detected in the only Xlinkage dominant transmission family, was a novel mutation. One mutation (3.3%) in the exon 3 of MPZ gene was identified in a CMT1 family. There were no PMP22 gene mutations in these patients. Conclusions About 16.7% CMT had point mutations in the Cx32, MPZ and PMP22 genes, and the mutations mainly belonged to Cx32 gene mutations. Mutational screening had to start with Cx32 gene in the possible Xlinkage family (especially if no maletomale transmission was observed).The low prevalence of Chinese CMT might be due to the different point mutations in these genes.