Congenital muscular dystrophy and congenital myopathy

Gene: JAG2

Green List (high evidence)

Coppens et al described 23 patients from 13 unrelated families with bi-allelic JAG2 variants (missense, nonsense, frameshift, in-frame deletion, and a microdeletion). Onset of muscle weakness ranges from infancy to young adulthood. Muscle histology was primarily dystrophic. MRI shows distinct pattern of muscle involvement. Functional studies shows that Jag2 downregulation cause downregulation of Notch pathway.

Created: 10 Nov 2022, 3:49 p.m. | Last Modified: 10 Nov 2022, 3:49 p.m.

Panel Version: 2.31

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
muscular dystrophy

Publications

• 33861953

Mode of pathogenicity
Other

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 4:51 p.m. | Last Modified: 1 Feb 2023, 4:51 p.m.

Panel Version: 3.22

Comment on list classification: Promoting from grey to amber, but with a recommendation for a green rating at the next review. 13 cases reported with muscular dystrophy and variants in JAG2.

Created: 30 Jun 2021, 2:57 p.m. | Last Modified: 30 Jun 2021, 2:57 p.m.

Panel Version: 2.10

As expert reviewer states PMID: 33861953 (Coppens et al 2021) report 13 families with previously genetically unsolved muscular dystrophy in which rare homozygous or compound heterozygous JAG2 variants were identified by WES. Transcriptome analysis of muscle tissue from two participants suggested misregulation of genes involved in myogenesis, including PAX7.

Created: 30 Jun 2021, 2:55 p.m. | Last Modified: 30 Jun 2021, 2:55 p.m.

Panel Version: 2.8

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
muscular dystrophy, MONDO:0020121

Publications

• 33861953

Green List (high evidence)

Whole-exome sequencing identified 13 families with rare homozygous or compound heterozygous JAG2 variants. Bi-allelic variants include 10 missense variants that disrupt highly conserved amino acids, a nonsense variant, two frameshift variants, an in-frame deletion, and a microdeletion encompassing JAG2. Onset of muscle weakness occurred from infancy to young adulthood. Serum creatine kinase (CK) levels were normal or mildly elevated. Muscle histology was primarily dystrophic. MRI of the lower extremities revealed a distinct, slightly asymmetric pattern of muscle involvement with cores of preserved and affected muscles in quadriceps and tibialis anterior, in some cases resembling patterns seen in POGLUT1-associated muscular dystrophy.
Sources: Literature

Created: 10 May 2021, 10:21 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
muscular dystrophy

Publications

• 33861953

Variants in this GENE are reported as part of current diagnostic practice