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

Shanshan Gao1, Abigail Mumme-Monheit1, Suet Nee Chen1

  • 1Divison of Cardiology, Cardiovascular Institute, University of Colorado, Aurora, Colorado, USA.

American Journal of Medical Genetics. Part A
|October 15, 2021
PubMed

Insights

A novel synonymous variant in the lamin A/C (LMNA) gene was found to cause severe dilated cardiomyopathy (DCM) by reducing LMNA mRNA levels. This discovery offers new insights into the genetic causes of DCM.

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.

Keywords:
LMNAdilated cardiomyopathygenotype phenotypesynonymous variant

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