一个巨脑性白质脑病伴皮层下囊肿家系的遗传分析及产前诊断

Genetic analysis and prenatal diagnosis for a family with megalencephalic leukoencephalopathy and subcortical cysts

目的对1个巨脑性白质脑病伴皮层下囊肿（megalencephalicleukoencephalopathywithsubcorticalcysts，MI。c）家系进行遗传分析并对高危胎儿进行产前诊断。方法应用PCR扩增MLCl基因的12个外显子及侧翼序列，对产物直接进行测序以寻找致病基因突变。选取1个短串联重复序列位点作为连锁分析遗传标记，结合DNA测序对胎儿进行产前诊断。结果家系中患者MLCj基因检测到1个缺失突变C．177_178delG（P．Ser60AlafsX5）和一个剪切位点突变C．598—2A〉C，后者为一种新突变，国际上尚未见报道。胎儿继承了父源性C－77—178delG突变，但未继承母源性C．598—2A〉C突变，与家系内1名表型正常的成员基因型一致。连锁分析结果与基因突变检测结果相符合。胎儿出生后表型正常，重新取材检测与产前诊断结果一致。结论发现了1种新的MLCI基因突变，为国内首次针对MLC家系开展的基因诊断，对于同类病例的遗传咨询、基因诊断和产前诊断具有借鉴意义。

Objective To identify potential mutation in the MLC1 gene in a Chinese family affected with megalencephalic leukoencephalopathy and subeortical cysts （MLC）, and to provide prenatal diagnosis. Methods Genomic DNA of the patients, their parents and younger sister were extracted from peripheral blood. That of the fetus was extracted from an amniotic fluid sample. A total of 12 exons and at least 100 hp flanking the intronic sequence of the MLC1 gene were amplified with PCR. MLC1 mutations were screened by sequencing. Linkage analysis was performed for the family to assure accuracy of prenatal diagnosis. Results The two patients were both heterozygote for c. 177_178delG （p. Ser60AlafsXS） mutation in exon 2 and c. 598-2A^C change in intron 7. The e. 177_178delG mutation was inherited from the father, and the e. 598-2A：〉C mutation was inherited from the mother. The younger sister and the fetus have both inherited c. 177 178delG from the father but did not inherit e. 598-2A〉C from the mother, Prenatal diagnosis suggested the fetus to be a carrier for a MLCl mutation. Linkage analysis was consistent with the result of mutation detection. The fetus was born normal as predicted. Conclusion The c. 598-2A〉C is a novel splicing mutation. Prenatal diagnosis through DNA sequencing and linkage analysis were performed for the first time on Chinese patients with MLC.