A splicing LMNA mutation causing laminopathies accompanied by aortic valve malformation.

Area of Science:

• Genetics
• Cardiology
• Neuromuscular Disorders

Background:

• Laminopathies, caused by LMNA gene mutations, present with diverse clinical features, notably severe cardiac involvement.
• LMNA gene mutations are associated with various phenotypes, including cardiomyopathy and muscular dystrophy.

Observation:

• A 30-year-old male presented with palpitations, dyspnea, fatigue, muscular dystrophy, joint contractures, scoliosis, and dysphagia.
• Genetic analysis revealed a novel de novo heterozygous LMNA splice variant (c.810+1G>T).
• The patient exhibited dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy, progressive cardiac conduction defect, and a congenital aortic valve malformation, a previously unreported association.

Findings:

• Identification of a novel de novo heterozygous LMNA splice variant (c.810+1G>T).
• This variant is associated with a complex phenotype including dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy, and progressive cardiac conduction defects.
• The study reports the first instance of congenital aortic valve malformation in a patient with an LMNA mutation.

Implications:

• The identified LMNA mutation (c.810+1G>T) expands the known mutation spectrum for laminopathies.
• The unexpected association of congenital aortic valve malformation with this LMNA mutation warrants further investigation.
• Understanding this genotype-phenotype correlation can improve diagnosis and management of laminopathies.