伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病NOTCH3基因突变的研究(附1家系报告)

Study of NOTCH 3 gene mutation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy( report of 1 family)

目的分析伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病(CADASIL)一家系罕见的NOTCH3基因突变及诊断方法。方法回顾性分析1例CADASIL先证者的临床资料并进行家系调查。结果本例先证者主要表现为脑卒中反复发作及认知障碍。先证者及其姐姐既往均采用Sanger法对NOTCH3基因突变热区进行基因测序,未检测到基因突变;而采用高通量测序法检测后发现NOTCH3基因第20号外显子存在一杂合错义突变(c.3226C>T)。家系中现存3例患者及其子女均采用高通量测序法检测出此突变基因。家系调查显示为常染色体显性遗传。结论 NOTCH3基因第20号外显子的杂合错义突变(c.3226C>T)为该家系的致病因素,高通量测序法能更全面发现罕见突变基因,减少漏诊。

Objective To analyze the scarce NOTCH3 gene mutation and diagnostic methods of a family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy（ CADASIL）. Methods The clinical data of a CADASIL patient was retrospectively analyzed,and the family of this patient was investigated.Results The main clinical manifestations of this patient were repeated episodes of stroke and cognitive impairment.The NOTCT3 gene mutation of this patient and her sister were never found by Sanger sequencing at past. While highthroughput sequencing revealed that a heterozygous missense mutation in exon 20 of NOTCH3 gene（ c. 3226 C T）was found in the two patients. The 3 CADASIL patients in this family and their children were all carried this mutation gene. The pedigree investigation showed autosomal dominant inheritance. Conclusions The heterozygous missense mutation（ c. 3226 C T） in exon 20 of NOTCH3 gene is the pathogenic factor for this family. High-throughput sequencing can find scarce mutant gene more comprehensively,and can reduce the missed diagnosis.