Guidetti D, Casali B, Mazzei R L, Cenacchi G, De Berti G, Zuccoli G, Nicoli D, Conforti F L, Sprovieri T, Pasquinelli G, Brini M
Division of Neurology, Santa Maria Nuova Hospital, Viale Risorgimento 80, I-42100, Reggio Emilia, Italy.
Neurol Sci. 2004 Feb;24(6):401-6. doi: 10.1007/s10072-003-0196-x.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is commonly overlooked or misdiagnosed owing to its recent identification. It is characterized clinically by recurrent cerebral infarcts, usually appearing between the ages of 30 and 50 years, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in approximately one-third of patients. The pathological hallmark of angiopathy is the presence of characteristic granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells. The defective gene in CADASIL is Notch3, which encodes a large transmembrane receptor, and 70% of missense mutations are in exons 3 and 4. Each gene defect leads to either a gain or loss of a cysteine residue in the extracellular N-terminal domain of the molecule. We report the case of a 53-year-old woman admitted to the hospital for transient ischemic attack and stroke-like episodes recurrent since age 43 years. The patient had pseudobulbar palsy, pyramidal signs, and cognitive impairment but not frank dementia. Cerebral MRI showed periventricular diffuse and confluent ischemic lesions. Ultrastructural study revealed an abnormal deposition of granular osmiophilic material (GOM) within the basal lamina in skin capillaries. Direct sequence analysis of the Notch3 gene was performed. Since no mutation was detected in exons 3 and 4, the remaining exons were sequenced and a missense mutation, CGC-TGC in codon 1006 of exon 19 was found. The mutation led to a gain of a cysteine residue. This is the first missense mutation in codon 1006 of exon 19 of the Notch3 gene to be described in Italy and the second reported in the literature.
伴有皮质下梗死和白质脑病的脑常染色体显性动脉病（CADASIL）由于其近期才被发现，常被忽视或误诊。其临床特征为反复发生脑梗死，通常出现在30至50岁之间，伴有皮质下痴呆和假性延髓麻痹。约三分之一的患者以伴有先兆的偏头痛为首发症状。血管病的病理特征是平滑肌细胞基膜内存在特征性的嗜锇颗粒物质（GOM）。CADASIL的缺陷基因是Notch3，它编码一种大型跨膜受体，70%的错义突变位于外显子3和4。每个基因缺陷都会导致分子细胞外N端结构域中半胱氨酸残基的增加或减少。我们报告了一例53岁女性患者，因短暂性脑缺血发作和自43岁起反复发作的类似中风症状入院。该患者有假性延髓麻痹、锥体束征和认知障碍，但无明显痴呆。脑部MRI显示脑室周围弥漫性融合性缺血性病变。超微结构研究显示皮肤毛细血管基膜内有嗜锇颗粒物质（GOM）异常沉积。对Notch3基因进行了直接测序分析。由于在外显子3和4中未检测到突变，因此对其余外显子进行了测序，发现外显子19的第1006密码子存在错义突变CGC-TGC。该突变导致半胱氨酸残基增加。这是意大利首次报道的Notch3基因外显子19第1006密码子的错义突变，也是文献中报道的第二例。
