Case Report: An Atypical Form of Familial Partial Lipodystrophy Type 2 Due to Mutation in the Rod Domain of Lamin A/C.

Abstract

Purpose:

Familial partial lipodystrophy type 2 (FPLD2) patients generally develop a wide variety of severe metabolic complications. However, they are not usually affected by primary cardiomyopathy and conduction system disturbances, although a few cases of FPLD2 and cardiomyopathy have been reported in the literature. These were all due to amino-terminal heterozygous lamin A/C mutations, which are considered as new forms of overlapping syndromes.

Methods and Results:

Here we report the identification of a female patient with FPLD2 due to a heterozygous missense variant c.604G>A in the exon 3 of the LMNA gene, leading to amino acid substitution (p.Glu202Lys) in the central alpha-helical rod domain of lamin A/C with a high propensity to form coiled-coil dimers. The patient's cardiac evaluations that followed the genetic diagnosis revealed cardiac rhythm disturbances which were promptly treated pharmacologically.

Conclusions:

This report supports the idea that there are "atypical forms" of FPLD2 with cardiomyopathy, especially when a pathogenic variant affects the lamin A/C head or alpha-helical rod domain. It also highlights how increased understanding of the genotype-phenotype correlation could help clinicians to schedule personalized monitoring of the lipodystrophic patient, in order to prevent uncommon but possible devastating manifestations, including arrhythmias and sudden death.

• Authors: Carolina Cecchetti, M Rosaria D'Apice, Elena Morini, Giuseppe Novelli, Carmine Pizzi, Uberto Pagotto, Alessandra Gambineri
• Journal: Frontiers in endocrinology (Front Endocrinol (Lausanne)) Vol. 12 Pg. 675096 ( 2021) ISSN: 1664-2392 [Print] Switzerland
• PMID: 33953703 (Publication Type: Case Reports)
• Copyright: Copyright © 2021 Cecchetti, D’Apice, Morini, Novelli, Pizzi, Pagotto and Gambineri.

Chemical References

• LMNA protein, human
• Lamin Type A
• Lamins
• lamin C protein, human

Topics

• Adult
• Female
• Genetic Association Studies
• Humans
• Lamin Type A (genetics)
• Lamins (genetics)
• Lipodystrophy, Familial Partial (genetics, pathology)
• Mutation, Missense
• Prognosis