Hung Ling Yin, Ling Tsz Ki, Lau Nike Kwai Cheung, Cheung Wing Lan, Chong Yeow Kuan, Sheng Bun, Kwok King Ming, Mak Chloe Miu
Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong Special Administrative Region.
Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region.
J Clin Neurosci. 2018 Oct;56:95-100. doi: 10.1016/j.jocn.2018.06.050. Epub 2018 Jul 3.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult onset hereditary stroke syndrome characterized by recurrent stroke and progressive cognitive impairment caused by NOTCH3 mutations. We report here the clinical and molecular findings of three unrelated Hong Kong Chinese families with CADASIL syndrome. Sanger sequencing of genomic DNA revealed a novel heterozygous variant NM_000435.2(NOTCH3):c.[5903_5904insATAA];[5903_5904=] NP_000426.2:p.(Asp1969);(Asp1969=) and two previously reported heterozygous mutations NM_000435.2(NOTCH3):c.[328C>T];[328C=] NP_000426.2:p.[(Arg110Cys)];[(Arg110=)] and NM_000435.2(NOTCH3):c.[580T>A];[580T=] NP_000426.2:p.(Cys194Ser);(Cys194=) in the three families respectively. Molecular basis of CADASIL in these three patients were further established. Genetic analysis provides a reliable method for confirming the diagnosis of CADASIL and enables proper genetic counseling and cascade testing.
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）是一种成年起病的遗传性中风综合征，其特征为NOTCH3突变导致复发性中风和进行性认知障碍。我们在此报告三个不相关的患有CADASIL综合征的中国香港家庭的临床和分子学发现。对基因组DNA进行桑格测序，分别在这三个家庭中发现了一个新的杂合变异NM_000435.2(NOTCH3):c.[5903_5904insATAA];[5903_5904=] NP_000426.2:p.(Asp1969);(Asp1969=)以及两个先前报道的杂合突变NM_000435.2(NOTCH3):c.[328C>T];[328C=] NP_000426.2:p.[(Arg110Cys)];[(Arg110=)]和NM_000435.2(NOTCH3):c.[580T>A];[580T=] NP_000426.2:p.(Cys194Ser);(Cys194=)。这三位患者CADASIL的分子基础得以进一步确立。基因分析为确诊CADASIL提供了一种可靠的方法，并能进行适当的遗传咨询和级联检测。
