Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy revisited
Open Access
- 1 June 2020
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology Genetics
- Vol. 6 (3), e434
- https://doi.org/10.1212/nxg.0000000000000434
Abstract
Objective The aim of this study was to evaluate the correlation between the various NOTCH3 mutations and their clinical and genetic profile, along with the presentation of a novel mutation in a patient. Methods Here, we describe the phenotype of a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) harboring a novel mutation. We also performed an extensive literature research for NOTCH3 mutations published since the identification of the gene and performed a systematic review of all published cases with NOTCH3 mutations. We evaluated the mutation pathogenicity in a great number of patients with detailed clinical and genetic evaluation and investigated the possible phenotype-genotype correlations. Results Our patient harbored a novel mutation in the NOTCH3 gene, the c.3084 G > C, corresponding to the aminoacidic substitution p.Trp1028Cys, presenting with seizures as the first neurologic manifestation. We managed to find a correlation between the pathogenicity of mutations, severity of the phenotype, and age at onset of CADASIL. Significant differences were also identified between men and women regarding the phenotype severity. Conclusions The collection and analysis of these scarce data published since the identification of NOTCH3 qualitatively by means of a systematic review and quantitatively regarding genetic profile and pathogenicity scores, highlight the significance of the ongoing trend of investigating phenotypic genotypic correlations.Keywords
This publication has 39 references indexed in Scilit:
- Role of Electron Microscopy in the Diagnosis of Cadasil Syndrome: A Study of 32 PatientsPLOS ONE, 2013
- Effects of Gender on the Phenotype of CADASILStroke, 2012
- NOTCH3 mutations and clinical features in 33 mainland Chinese families with CADASILJournal of Neurology, Neurosurgery & Psychiatry, 2010
- Distinct phenotypic and functional features of CADASIL mutations in the Notch3 ligand binding domainBrain, 2009
- Congruence between NOTCH3 mutations and GOM in 131 CADASIL patientsBrain, 2009
- Skin biopsy findings and results of neuropsychological testing in the first confirmed cases of CADASIL in NorwayEuropean Journal of Neurology, 2006
- The spectrum of mutations for CADASIL diagnosisNeurological Sciences, 2005
- Retinal abnormalities in CADASIL: a retrospective study of 18 patientsJournal of Neurology, Neurosurgery & Psychiatry, 2004
- Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementiaNature, 1996
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12Nature Genetics, 1993