兄弟同患多发性皮肤平滑肌瘤及其延胡索酸水合酶基因突变的分析

Mutation Analysis of the Fumarate Hydratase Gene in Two Brothers with Multiple Cutaneous Leiomyomas

目的检测一对多发性皮肤平滑肌瘤兄弟延胡索酸水合酶(fumarate hydratase,FH)基因外显子突变情况,以明确其致病突变。方法收集患病兄弟的临床资料,提取其外周血DNA,通过PCR扩增FH基因编码区的全部外显子(n=10)并测序,以10例健康志愿者为对照。结果发现该兄弟均存在FH基因外显子7(c.927G>GA)的无义杂合突变(p.P309P)和外显子9(c.1256C>CT)错义杂合突变(p.S419L),其中前者是已知的突变位点,后者是新发现位点的突变。对照组均未发现上述位点的突变。结论外显子9(1256C>CT)的错义突变可能是导致兄弟俩临床表型的原因,为该病的基因突变研究增加新的数据。

Objective To detect mutations in the fumarate hydratase （FH） gene in two brothers with muhiple cutane- ous leiomyomas. Methods Clinical data was collected from a 37-year-old patient and his younger brother. Peripheral blood was obtained from two patients and 10 healthy controls. All the ten exons in the FH gene were amplified by PCR and examined by direct DNA sequencing. Results Heterozygous nonsense mutation of c. 927G 〉 GA （p. P309P） in exon 7 and missense mutation of c. 1256C 〉 T（p. S419L） in exon 9 of FH gene were found in two brother with multiple cutaneous leiomyomas, respectively. No such mutations were detected in wild-type FH gene from the healthy controls. Conclusion The missense mutation c. 1256C 〉 CT in exon 9 of FH gene might contribute to the phenotype of patients manifested as multiple cutaneous leiomyomas.