Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: CAPN3

Green List (high evidence)

Classified as LIMITED for AD association with LGMD and DEFINITIVE for AR association with LGMD by ClinGen Muscular Dystrophies and Myopathies on 29/08/2024.

AD association has been reported in at least 4 unrelated probands. The mechanism of disease for AD LGMD is still not not established however AR appears to be loss of function.

AR - https://search.clinicalgenome.org/CCID:004339
AD - https://search.clinicalgenome.org/CCID:004338

Created: 6 Sep 2024, 1:51 a.m. | Last Modified: 6 Sep 2024, 1:51 a.m.

Panel Version: 1.37

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
muscular dystrophy, limb-girdle, autosomal dominant MONDO:0015151; autosomal recessive limb-girdle muscular dystrophy MONDO:0015152

Green List (high evidence)

AD calpainopathies are rare, however there are emerging reports in recent literature of heterozygous variants segregating with disease in families, including at least 6 missense and 2 small in-frame deletions (PMID: 32557990). These variants are associated with a milder calpainopathy phenotype than patients with recessive LoF variants, and some carriers only present with isolated hyperCKaemia. In general, the AD variants have been associated with milder and later-onset phenotypes (PMID: 32342993).

Created: 9 Oct 2020, 4:01 a.m. | Last Modified: 9 Oct 2020, 4:01 a.m.

Panel Version: 0.55

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
CAPN3-related muscular dystrophy, AD, AR

Publications

• 32557990
• 32342993

Green List (high evidence)

PMID: 31937337 - 15 families with limb girdle muscular dystrophy. 13/15 report childhood onset in multiple affected children, where EMG confirmed a myopathic disorder, with mild-severe dystrophic changes. Note recurrent 21bp deletion associated with dominant LGMD.

Created: 24 Jun 2020, 1:26 p.m. | Last Modified: 24 Jun 2020, 1:26 p.m.

Panel Version: 0.14

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy, limb-girdle, autosomal dominant 4, MIM# 618129; Muscular dystrophy, limb-girdle, autosomal recessive 1, MIM# 253600

Publications

• 31937337
• 28881388

Green List (high evidence)

PMID: 31937337 - 15 families with limb girdle muscular dystrophy. 13/15 report childhood onset in multiple affected children, where EMG confirmed a myopathic disorder, with mild-severe dystrophic changes.
Sources: Literature

Created: 24 Jun 2020, 6:06 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy, limb-girdle, autosomal recessive 1 253600

Publications

• PMID: 31937337