SGCD – Dilated Cardiomyopathy

In a cohort of 21 ICD-implanted dilated cardiomyopathy (DCM) patients undergoing next-generation sequencing of 15 cardiomyopathy-associated genes, 29% harbored variants in TPM1, TNNT2, MYH7, PLN, or MYBPC3, while no SGCD variants were identified, indicating minimal contribution of SGCD to human DCM (PMID:31179125). No segregation data support SGCD causality in familial DCM.

Functional assessment of the SGCD c.451T>G (p.Ser151Ala) variant in heterozygous knock-in mice yielded a mild subclinical cardiomyopathy characterized by increased heart-to-body weight ratio, preserved function, and absent histopathology at one year; AAV9-mediated cardiac expression of p.Ser151Ala SGCD partially restored function, suggesting a hypomorphic effect rather than complete loss-of-function (PMID:23695275). Given the absence of human pathogenic variants and the mild murine phenotype, the SGCD–DCM association is classified as Limited. Key take-home: SGCD variants currently lack evidence for clinical genetic testing in DCM.

References

• Cardiology research and practice • 2019 • Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing? PMID:31179125
• European journal of human genetics • 2014 • S151A δ-sarcoglycan mutation causes a mild phenotype of cardiomyopathy in mice PMID:23695275

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