Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies

Gene: JAG2

Green List (high evidence)

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

Created: 11 Dec 2025, 10:47 a.m. | Last Modified: 11 Dec 2025, 10:47 a.m.

Panel Version: 5.24

Green List (high evidence)

Comment on list classification: As reviewed by Lauren Turton, there is sufficient evidence available (16 unrelated families) for the association of JAG2 with Limb-girdle muscular dystrophy-27 (MIM #619566). Hence, this gene should be promoted to green rating in the next GMS update.

Created: 1 May 2025, 4:53 p.m. | Last Modified: 1 May 2025, 4:53 p.m.

Panel Version: 5.3

PMID:33861953 reported the identification of either homozygous or compound heterozygous variants in JAG2 gene in 23 individuals from 13 unrelated families with muscular dystrophy. The identified bi-allelic variants include 10 missense variants, a nonsense variant, two frameshift variants and an in-frame deletion. An individual was compound heterozygous for a single nucleotide variant and a microdeletion encompassing JAG2. The families were of various ethnic descents, ranged in age from 5 to 53 years and had a variable age at onset of the disorder; 5 had onset in infancy, 9 in childhood, and 9 in adolescence or young adulthood. Most presented with slowly progressive muscle weakness of the proximal lower limbs, although the patients with infantile onset showed delayed motor development and more rapid disease progression. Eight patients lost ambulation between 8 and 18 years of age.

PMID:39121631 reported three patients from two different Australian families with three novel JAG2 missense variants: Two siblings of Pakistani descent were identified with homozygous variant (1021G>T, p.(Gly341Cys)), while a proband of European descent was identified with compound heterozygous variants (c.703T>C, p.(Trp235Arg); c.2350C>T, p.(Arg784Cys)). These patients presented with childhood-onset limb-girdle-like myopathy with difficulty or inability walking.

PMID:39649397 reported two siblings of Tajik descent with limb-girdle muscular dystrophy. They were identified with a novel JAG2 homozygous frameshift variant [c.3467_3470dup, p.(Pro1158AlafsTer22)]. The parents are first-cousins and carried the variant in heterozygous state.

This gene has been associated with relevant phenotypes in both OMIM (MIM #619566) and Gene2Phenotype (with 'strong' rating on the DD panel).

Created: 1 May 2025, 4:50 p.m. | Last Modified: 1 May 2025, 4:50 p.m.

Panel Version: 5.1

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy, limb-girdle, autosomal recessive 27, OMIM:619566

Publications

• 33861953
• 39121631
• 39649397

Green List (high evidence)

This gene is currently green on the R79 congenital muscular dystrophy panel.
PMID: 33861953 initial paper on this gene. 23 patients from 13 unrelated families.
PMID: 39121631 three additional patients who presented with childhood onset limb girdle myopathy.
PMID: 39649397 two additional patients presenting with childhood onset muscle hypotonia predominantly affecting the pelvic girdle and proximal leg muscles.
Sources: NHS GMS

Created: 17 Apr 2025, 3:06 p.m. | Last Modified: 17 Apr 2025, 3:06 p.m.

Panel Version: 4.40

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Limb-girdle muscular dystrophy-27 (OMIM: 619566)

Publications

• 33861953
• 39121631
• 39649397

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