An LMNA synonymous variant associated with severe dilated cardiomyopathy: Case report

Area of Science:

• Genetics
• Cardiology
• Molecular Biology

Background:

• Dilated cardiomyopathy (DCM) is a common heart condition often linked to genetic mutations.
• Mutations in the lamin A/C (LMNA) gene are a known cause of human DCM.
• Understanding the molecular basis of DCM is crucial for diagnosis and treatment.

Observation:

• A cohort of 57 heart transplant patients with DCM was screened for LMNA gene variants.
• A novel synonymous variant, c.936G>A, was identified in the LMNA gene within a DCM family.
• Variant carriers exhibited severe familial DCM, conduction abnormalities, and elevated creatine kinase levels.

Findings:

• The LMNA c.936G>A variant was present in genomic DNA but absent in cDNA from heart tissue, indicating aberrant splicing.
• Quantitative PCR revealed significantly lower LMNA mRNA levels in patients with the variant compared to controls.
• This suggests the synonymous variant leads to reduced LMNA mRNA and potentially protein expression.

Implications:

• This study identifies a novel synonymous LMNA variant associated with DCM pathogenesis.
• The findings expand the understanding of how genetic variations in LMNA contribute to dilated cardiomyopathy.
• This research may aid in the genetic diagnosis and counseling of families affected by DCM.