C9ORF72 repeat expansions in cases with previously identified pathogenic mutations.

ABSTRACT:

Objective

To identify potential genetic modifiers contributing to the phenotypic variability that is detected in patients with repeat expansions in chromosome 9 open reading frame 72 (C9ORF72), we investigated the frequency of these expansions in a cohort of 334 subjects previously found to carry mutations in genes known to be associated with a spectrum of neurodegenerative diseases.

Methods

A 2-step protocol, with a fluorescent PCR and a repeat-primed PCR, was used to determine the presence of hexanucleotide expansions in C9ORF72. For one double mutant, we performed Southern blots to assess expansion sizes, and immunohistochemistry to characterize neuropathology.

Results

We detected C9ORF72 repeat expansions in 4 of 334 subjects (1.2% [or 1.8% of 217 families]). All

SUBMITTER: van Blitterswijk M 

PROVIDER: S-EPMC3806926 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature