Li Shufeng, Chen Yifan, Shan Haitao, Ma Fang, Shi Minke, Xue Jun
Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing 210009, China.
Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing 210009, China.
J Clin Neurosci. 2017 Dec;46:85-89. doi: 10.1016/j.jocn.2017.08.029. Epub 2017 Sep 1.
NOTCH3 mutations have been described to cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Here, we report 2 CADASIL patients from a Chinese family. Whole genome sequencing was performed on the two CADASIL patients. The novel variant c.128G>C in exon 2 of NOTCH3 was identified and confirmed through PCR-Sanger sequencing (Human Genome Variation Society nomenclature: HGVS: NOTCH3 c.128G>C; p.Cys43Ser). The heterozygous NOTCH3 variant cause a cysteine to serine substitution at codon 43. According to the variant interpretation guideline of American College of Medical Genetics and Genomics (ACMG), this variant was classified as "pathogenic". Other variants in HTRA1, COL4A1 and COL4A2 were also found, they were classified as "benign".
NOTCH3突变已被证实可导致伴有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）。在此，我们报告了来自一个中国家庭的2例CADASIL患者。对这2例CADASIL患者进行了全基因组测序。通过PCR-Sanger测序鉴定并确认了NOTCH3基因第2外显子中的新变异c.128G>C（人类基因组变异协会命名法：HGVS：NOTCH3 c.128G>C；p.Cys43Ser）。NOTCH3杂合变异导致第43密码子处的半胱氨酸被丝氨酸取代。根据美国医学遗传学与基因组学学会（ACMG）的变异解读指南，该变异被分类为“致病性”。此外还发现了HTRA1、COL4A1和COL4A2中的其他变异，它们被分类为“良性”。
