PDF(Pubmed)
Abstract：
Introduction: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal-dominant systemic vascular disease that primarily involves small arteries. Patients with CADASIL experience migraines, recurrent ischemic strokes, cognitive decline, and dementia. The NOTCH3 gene, which is located on chromosome 19p13.12, is one of the disease-causing genes in CADASIL. Herein, we investigate the genetic and phenotypic features in a Chinese CADASIL family with heterozygous NOTCH3 mutation. Methods and Results: In the family, the proband suffered from dizziness, stroke, and cognitive deficits. Brain magnetic resonance imaging (MRI) demonstrated symmetrical white matter lesions in the temporal lobe, outer capsule, lateral ventricle, and deep brain. Whole-exome sequencing identified a known missense mutation in the proband, c.397C>T (p.Arg133Cys), which was identified in his son and granddaughter using Sanger sequencing. The proband\'s younger brother and younger sister also have a history of cognitive impairment or cerebral infarction, but do not have this genetic mutation, which may highlight the impact of lifestyle on this neurological disease. Conclusion: We identified a known CADASIL-causing mutation NOTCH3 (c.397C>T, p.Arg133Cys) in a Chinese family. The clinical manifestations of mutation carriers in this family are highly heterogeneous, which is likely a common feature for the etiology of different mutations in CADASIL. Molecular genetic analyses are critical for accurate diagnosis, as well as the provision of genetic counselling for CADASIL.
摘要：
简介：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）是一种常染色体显性遗传性系统性血管疾病，主要累及小动脉。CADASIL患者有偏头痛，复发性缺血性中风，认知能力下降,和痴呆症。NOTCH3基因，位于染色体19p13.12上，是CADASIL中的致病基因之一。在这里，我们研究了具有杂合NOTCH3突变的中国CADASIL家族的遗传和表型特征。方法和结果:在家庭中,先证者头晕,中风,和认知缺陷。脑磁共振成像（MRI）显示颞叶对称白质病变，外囊,侧脑室,和深层大脑。全外显子组测序确定了先证者中已知的错义突变，c.397C>T（p。Arg133Cys)，在他的儿子和孙女中使用Sanger测序鉴定。先证者的弟弟和妹妹也有认知障碍或脑梗塞的病史，但是没有这种基因突变，这可能凸显了生活方式对这种神经系统疾病的影响。结论：我们确定了一个已知的CADASIL引起的突变NOTCH3（c.397C>T，p.Arg133Cys）在一个中国家庭。该家族中突变携带者的临床表现具有高度异质性，这可能是CADASIL中不同突变的病因的共同特征。分子遗传学分析对于准确诊断至关重要，以及为CADASIL提供遗传咨询。
