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Research Article: A Family with a Single LMNA Mutation Illustrates Diversity in Cardiac Phenotypes Associated with Laminopathic Progeroid Syndromes

Date Published: 2023-09-26

Abstract:
The likely pathogenic variant c.407A>T p.Asp136Val of the LMNA gene has been recently described in a young woman presenting with atypical progeroid syndrome, associated with severe aortic valve stenosis. We further describe the cardiovascular involvement associated with the syndrome in her family. We identified seven members with a general presentation suggestive of progeroid syndrome. All of them presented heart conduction abnormalities: degenerative cardiac diseases such as coronary artery disease (two subjects) and aortic stenosis (three subjects) occurred in the 3rd–5th decade, and a young patient developed a severe dilated cardiomyopathy, leading to death at 15 years of age. The likely pathogenic variant was found in all the patients who consented to carry out the genetic test. This diverse family cardiologic phenotype emphasizes the complex molecular background at play in lamin-involved cardiac diseases, and the need for early and thorough cardiac evaluations in patients with laminopathic progeroid syndromes.

Introduction:
The LMNA gene consists of approximately 24 kb and 12 exons. The alternative splicing of exon 10 results in two major isoforms, lamin A and lamin C. Lamins A/C belong to the intermediate filament protein family and are components of the nuclear lamina, a fibrous layer located near the inner nuclear membrane. They are present in equal amounts in the lamina of mammals. Their various functions include nuclear structural support, the anchoring of nuclear pores, chromatin and protein binding, and mechanotransduction.…

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