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BMC Neurology

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Open Access 01-12-2020 | Migraine | Case report

Homozygous NOTCH3 p.R587C mutation in Chinese patients with CADASIL: a case report

Authors: Ruojie He, Huan Li, Yiming Sun, Menglong Chen, Liang Wang, Yuling Zhu, Cheng Zhang

Published in: BMC Neurology | Issue 1/2020

Abstract

Background

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused by mutations in NOTCH3 gene with remarkable phenotypic heterogeneity. Cases of CADASIL associated with homozygous NOTCH3 mutations are rare and subsequently understudied. In this study, we investigate the genetic and phenotypic features within patients of CADASIL with homozygous NOTCH3 mutations.

Case presentation

We recruited two affected individuals with CADASIL from a mainland Chinese family. The proband (Patient 1), a 60-year-old male, presented with slow progressive gait instability, severe cognitive impairment, and emotional disorder for more than 2 years with a history of ischemic stroke and hypertension. His younger brother (Patient 2) presented with apparent gait difficulties, dysarthria as well as cognitive decline at 59 years old. Brain magnetic resonance imaging (MRI) showed diffused white matter lesions involving bilateral periventricular white matter, semioval center region, and anterior temporal lobes. Molecular genetic testing identified a homozygous variant, c.1759C > T (p.R587C), in NOTCH3 gene in both patients. Pathological analysis revealed granular osmiophilic material (GOM) deposits in small arterial walls of skin from the proband. The diagnosis of CADASIL was confirmed.

Conclusions

Our cases of CADASIL with homozygous mutation c.1759C > T (p.R587C) in NOTCH3 share similar manifestation to the patients with heterozygous same mutation reported previously. Other than genetic factors, vascular risk factors or environmental factors might contribute to the phenotypic variation of CADASIL.

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Title: Homozygous NOTCH3 p.R587C mutation in Chinese patients with CADASIL: a case report
Authors: Ruojie He
Huan Li
Yiming Sun
Menglong Chen
Liang Wang
Yuling Zhu
Cheng Zhang
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Migraine
CADASIL
Published in: BMC Neurology / Issue 1/2020
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-020-01660-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Homozygous NOTCH3 p.R587C mutation in Chinese patients with CADASIL: a case report

Abstract

Background

Case presentation

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Case presentation

Conclusions

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