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目的 报告 4个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)家系的NOTCH3基因突变特点。方法 对 4个经临床和病理检查证实的CADASIL家系中的先证者作NOTCH3基因编码区外显子 1～ 12的聚合酶链反应 (PCR)和DNA测序 ,对家系 2和 4中的部分亲属也作了同样的检查。结果 4个家系中的先证者均发现有NOTCH3基因的杂合性错义突变 ,先证者 1为外显子 3的 2 6 8C→T突变 ,先证者 2为外显子 3的 32 2C→T突变 ,先证者 3为外显子 3的 32 8C→T突变 ,先证者 4为外显子 11的 1819C→T突变 ,分别造成Notch3蛋白质R90C、C10 8R、R110C和R6 0 7C 4个位点氨基酸的替换。其中先证者 2的C10 8R突变尚未见文献报道。在家系 2和家系 4中 ,部分成员也携带与先证者同样的突变。结论 这 4个家系的CADASIL病均由NOTCH3基因的突变引起 ,不同位点的基因突变导致相似的临床表现
Objective To report the characteristics of the NOTCH3 gene mutation in four pedigrees of autosomal dominant cerebral artery disease (CADASIL) with subcortical infarcts and leukoencephalopathy. Methods Polymerase chain reaction (PCR) and DNA sequencing of exon 1 to 12 in the coding region of NOTCH3 gene were performed on four probands of CADASIL pedigree confirmed by clinical and pathological examinations. Some relatives in families 2 and 4 Also made the same inspection. Results All the probands in four families found a heterozygous missense mutation of NOTCH3 gene, proband 1 was the 268C → T mutation of exon 3, proband 2 was 32 of exon 3 2C → T mutation, proband 3 is 32 8C → T mutation of exon 3, proband 4 is 1819C → T mutation of exon 11, causing Notch3 proteins R90C, C10 8R, R110C and R6 0 7C, respectively 4 sites amino acid replacement. Which the proband 2 C10 8R mutation has not been reported in the literature. In Family 2 and Family 4, some members also carry the same mutation as the proband. CONCLUSIONS: CADASIL disease in these four pedigrees is caused by a mutation in the NOTCH3 gene. Mutations at different loci lead to similar clinical manifestations