Archetypal NOTCH3 mutations frequent in public exome: implications for CADASIL.

ABSTRACT:

Objective

To determine the frequency of distinctive EGFr cysteine altering NOTCH3 mutations in the 60,706 exomes of the exome aggregation consortium (ExAC) database.

Methods

ExAC was queried for mutations distinctive for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), namely mutations leading to a cysteine amino acid change in one of the 34 EGFr domains of NOTCH3. The genotype-phenotype correlation predicted by the ExAC data was tested in an independent cohort of Dutch CADASIL patients using quantified MRI lesions. The Dutch CADASIL registry was probed for paucisymptomatic individuals older than 70 years.

Results

We identified 206 EGFr cysteine altering NOTCH3 mutations in ExAC, with a total prevalenc

SUBMITTER: Rutten JW 

PROVIDER: S-EPMC5099530 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature