Paediatric or syndromic cardiomyopathy

Gene: SGCG

Green List (high evidence)

Comment on list classification: There are >20 unrelated patients reported with biallelic SGCG variants and with 'Muscular dystrophy, limb-girdle, autosomal recessive 5' (MIM #253700). However, the disease has a variable presentation and cardiomyopathy was reported only in a subset of patients. Five different variants (two frameshift and three missense variants) were identified in these patients with cardiac phenotypes, including the p.Cys283Tyr founder variant in Gypsies.

There is also functional evidence from mice model, which supports the association of SGCG gene with cardiomyopathy.

As this panel includes syndromic cases, this gene can be considered for promotion to green rating in the next GMS update.

Created: 26 Aug 2025, 6:13 p.m. | Last Modified: 26 Aug 2025, 6:23 p.m.

Panel Version: 7.34

Comment on phenotypes: OMIM phenotype accessed on 26 August 2025.

Created: 26 Aug 2025, 6:01 p.m. | Last Modified: 26 Aug 2025, 6:01 p.m.

Panel Version: 7.32

PMID:10942431 (2000) reported two siblings of Middle Eastern descent with autosomal recessive limb-girdle muscular dystrophy (LGMDR5), of which one of them presented with dilated cardiomyopathy. Both siblings were identified with a homozygous frameshift variant in SGCG gene (c.525delT).

PMID:11053682 (2000) reported a homogeneous group of 10 gypsy patients from three kindreds with a homozygous founder variant (c.848G>A/ p.Cys283Tyr) in SGCG gene. While all 10 had severe limb-girdle muscular dystrophy, right ventricle free wall hypertrophy and/or dilatation was found in six of these patients, and four of the older patients had early signs of right ventricular dysfunction.

PMID:24464767 (2014) reported the retrospective analysis of 19 patients, of which 11 patients were reported with SGCG-related LGMDR5 and 8 were reported with SGCA-related LGMDR3. All but one patient with gamma-sarcoglycanopathy harboured c.525delT variant, and one patient had c.525delT variant. Five of these 11 patients with LGMDR5 had left ventricular dysfunction (LVEF < 50%).

PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the 100,000 genomes project, of which one male patient with dilated cardiomyopathy was identified with compound heterozygous missense variants in SGCG gene (c.158T>C/ p.Leu53Pro & c.787G>A/ p.Glu263Lys), of which c.787G>A variant was proven to be inherited.

This gene has been associated with Muscular dystrophy, limb-girdle, autosomal recessive 5 (MIM #253700) in OMIM, which also records cardiac involvement in a subset of patients as relevant clinical presentation (abnormal precordial tall R waves on EKG, right ventricular hypertrophy and right ventricular dilatation).

PMID:14991064 provided functional evidence from Sgcg knockout mice, which develop a progressive cardiomyopathy characterised by focal myocardial degeneration and fibrosis. Transgenic rescue experiments in mice showed that re-expressing SGCG only in cardiac muscle (but not in vascular muscle) was sufficient to prevent the cardiomyopathy in Sgcg-null mice.
Sources: Literature

Created: 26 Aug 2025, 6:01 p.m. | Last Modified: 26 Aug 2025, 6:21 p.m.

Panel Version: 7.33

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy, limb-girdle, autosomal recessive 5, OMIM:253700; autosomal recessive limb-girdle muscular dystrophy type 2C, MONDO:0009677

Publications

• 10942431
• 11053682
• 14991064
• 24464767
• 39472908