巨脑性白质脑病伴皮层下囊肿一家系MLC1基因突变分析

目的通过对巨脑性白质脑病伴皮层下囊肿(MLC)一家系的分析,确定其MLC1基因的改变及遗传特征。方法收集先证者及其家系成员的临床资料,采用聚合酶链反应(PCR)和DNA直接测序方法进行MLC1基因突变检测,确定基因突变位点,明确MLC诊断。结果本家系先证者临床符合MLC诊断。测序结果发现两个基因位点改变c.218G>A(p.Gly73Glu)和IVS9-1G>C。患儿为复合杂合突变致病,其c.218G>A突变来自母亲,IVS9-1G>C突变来自父亲,其父母均为表型正常携带者。结论此家系中1例中国MLC患儿存在MLC1基因复合杂合突变,一个是错义突变,另一个是剪接位点突变。

Analysis of Megalencephalic Leukoencephalopathy with Subcortical Cysts 1 Gene Mutations in a Chinese Family with Megalencephalic Leukoencephalopathy with Subcortical Cysts

Objective Megalencephalic leukoencephalopathy with subcortical cysts(MLC) is an autosomal recessive disorder characterized by macrocephaly,deterioration of motor function with ataxia,spasticity and mental decline.Cranial magnetic resonance imaging(MRI) shows swollen brain with diffuse white-matter abnormalities and subcortical cysts,particularly in the anterior-temporal region.Mutation of MLC1 gene,which encodes a novel protein MLC1,has been identified as a cause of MLC.Since the first report,50 mutations in this gene have been found.But up to now,no case with MLC disease and the investigation of the MLC1 gene mutation has been reported in China.Here we reported a Chinese patient with MLC and the MLC1 gene mutation analysis in his family.Methods Genomic DNA from a Chinese patient and his parents were screened for mutations in the entire coding region,including the exon-intron boundaries,of the MLC1 gene.Results The patient was a compound heterozygote with two mutations,c.218G>A(p.Gly73Glu) inherited from his mother,and IVS9-1G>C inherited from his father.Both his parents were heterozygous carrier of 1 of those 2 mutations.Conclusions Variations of two MLC1 gene are identified in this Chinese patient with MLC,a missense mutation and a splice-site mutation.Both mutations have not been reported yet.This is the first reported Chinese MLC case,and the first one confirmed by MLC1 mutation analysis.