Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies

Gene: DUX4

I don't know

Review and rating from Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.

Created: 30 Apr 2019, 11:45 a.m.

Red List (low evidence)

Associated with FSHD

Created: 30 Apr 2019, 11:24 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Facioscapulohumeral muscular dystrophy, 158900

Red List (low evidence)

Rated as red because the mutation is currently NGS unreportable. The mutation is a contraction of the D4Z4 macrosatellite array in the subtelomeric region of chromosome 4q35 (normal = 11 to 150 repeat units, ~3.3Kb per unit; contracted = 1 to 10 repeat units). There are two haplotypes of the D4Z4: 4A and 4B. The contraction mutation of the D4Z4 array cause the FSHMD phenotype only when the mutation is on the 4A haplotype. Current diagnostic testing is carried out as follows: 1- the length or number of repeat units of the D4Z4 locus is determined by Southern blot analysis; 2- if a contraction is detected, 4A/4B haplotypes are determined to confirm that the contraction occurs on the 4A and avoid false positives

Created: 27 Mar 2017, 10:25 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Facioscapulohumeral muscular dystrophy, 158900

Mode of pathogenicity
Other