A case of recurrent intracranial hemorrhage in CADASIL caused by NOTCH3 c.1759C>T heterozygous mutation

Abstract

Background Cerebral autosomal‐dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebrovascular disease that is closely related to the NOTCH3 gene. Recurrent ischemic stroke, progressive cognitive dysfunction, and mental symptoms are the main clinical manifestations, whereas symptomatic intracranial hemorrhage is rare. Methods We detected a heterozygous mutation of c.1759C>T in exon 11 of the NOTCH3 gene that caused recurrent intracranial hemorrhage in CADASIL. Results Second‐generation sequencing of a sample of the patient's genome revealed a heterozygous mutation of c.1759C>T in exon 11 of NOTCH3 , which resulted in amino acid changes (p.R587C). This variation may be rated as a CADASIL clinical variation. Conclusion The discovery of this mutation site provides an important theoretical basis for a gene‐based diagnosis and treatment of recurrent intracranial hemorrhage.

Prevalence, clinical characteristics, and risk factors of intracerebral haemorrhage in CADASIL: a case series and systematic review

“…Thirty studies were eligible, including 21 case reports [ 16 – 36 ], 7 case series [ 13 , 14 , 37 – 41 ], and 2 observational studies [ 11 , 15 ], comprising 119 CADASIL patients with history of ICH. Half of the studies were published in Asia, which consisted of 98 cases (76.0%).…”