1例CADASIL家系的临床特征与基因突变分析

A case of CADASIL family with an unusual p.Cys194Arg mutation in exon 4 of the NOTCH3 gene

目的分析1例皖江地区CADASIL家系的临床表现及基因突变特征。方法随访记录1例CADASIL家系先证者的临床表现、实验室检查及影像学检查,对其NOTCH3基因突变热点区行基因检测。结果先证者为1例53岁男性患者,病程中反复发作脑卒中并有家族发病史,另表现假性球麻痹、情绪障碍、冷漠和轻度认知功能障碍,无偏头痛史。其头颅核磁共振显示对称性双侧颞极及外囊区白质高信号病变。患者NOTCH3基因突变分析发现4号外显子区已知致病突变(c.580T>C)和常见核苷酸多态性(rs1043994)。结论 c.580T>C突变是中国人CADASIL病例首次报道,基因检测是确诊CADASIL的金标准。

Objective To analysis the characteristic clinical manifestations and gene mutations of CA- DASIL pedigrees in Wanjiang Region. Methods We follow-up and record clinical manifestations, laboratory tests and imaging studies of CADASIL pedigree proband, comprehensive data analysis of these and their line NOTCH3 gene mutation hotspot detection. Results The patient was a 53-year-old man with a positive family for stroke. He presented with pseudobulbar palsy,mood disorders, apathy and mild cognitive impairment but no history of migraine. A cranial MRI revealed white matter hyperintensity involving the bilateral temporal lobes and the external capsule and microbleeds in the brainstem and the basal ganglia. Genetic analysis detected both a missense mutation, c. 580T, in codon 194 that results in the replacement of a cysteine residue with an ar- ginine, p. Cys194Arg, and rs1043994, a common polymorphism in the Caucasian population that has been rarely reported in Asian CADASIL patients. Conclusions This is the first report of the p. Cys194Arg mutation and the SNP rs1043994 in a Chinese CADASIL patient. Genetic testing is the gold standard for the diagnosis of CADASIL.