Intronic SMCHD1 variants in FSHD: testing the potential for CRISPR-Cas9 genome editing.

ABSTRACT:

Background

Facioscapulohumeral dystrophy (FSHD) is associated with partial chromatin relaxation of the DUX4 retrogene containing D4Z4 macrosatellite repeats on chromosome 4, and transcriptional de-repression of DUX4 in skeletal muscle. The common form of FSHD, FSHD1, is caused by a D4Z4 repeat array contraction. The less common form, FSHD2, is generally caused by heterozygous variants in SMCHD1.

Methods

We employed whole exome sequencing combined with Sanger sequencing to screen uncharacterised FSHD2 patients for extra-exonic SMCHD1 mutations. We also used CRISPR-Cas9 genome editing to repair a pathogenic intronic SMCHD1 variant from patient myoblasts.

Results

We identified intronic SMCHD1 variants in two FSHD families. In the

SUBMITTER: Goossens R 

PROVIDER: S-EPMC11578682 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature