Key result
LMNA p.Asp300Asn variant linked to severe early-onset valvular disease and CAD without systemic progeroid features.
Case Report
This case expands the clinical spectrum of the LMNA p.Asp300Asn variant to include nonsyndromic cardiac progeria with presumed gonadal mosaicism, emphasizing the need for genetic testing in unexplained early-onset cardiac disease.
May prompt LMNA testing in unexplained early-onset cardiac disease; extends variant spectrum but remains hypothesis-generating.
We describe the first genetically confirmed familial case of nonsyndromic cardiac progeria caused by the LMNA NM_170707.4:c.898G>A (p.Asp300Asn) variant, with evidence suggesting gonadal mosaicism as the mechanism of inheritance. The proband developed severe early-onset valvular and coronary artery disease requiring multiple surgical interventions, yet showed no systemic progeroid features. Genetic analysis revealed the heterozygous variant in her unaffected daughters and nieces but not in either parent. Comparison with previously reported cases highlights striking clinical heterogeneity associated with this variant, ranging from isolated cardiovascular involvement to syndromic progeroid manifestations with metabolic and skeletal abnormalities. This variability likely reflects the combined influence of genetic, epigenetic, and environmental factors. Our case expands the clinical spectrum of LMNA p.Asp300Asn and underscores the importance of considering laminopathies in patients with unexplained early-onset cardiac disease. Early genetic diagnosis is essential for the management, surveillance, and counseling of affected families.
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Nuzhnaya et al. (2025) conducted a case report in Nonsyndromic cardiac progeria. LMNA p.Asp300Asn variant was evaluated. The LMNA p.Asp300Asn variant was identified as the cause of severe early-onset valvular and coronary artery disease without systemic progeroid features in a familial case.
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