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Partial Lipodystrophy and LMNA p.R545H Variant

Laminopathies are disorders caused by LMNA gene mutations, which selectively affect different tissues and organ systems, and present with heterogeneous clinical and pathological traits. The molecular mechanisms behind these clinical differences and tissue specificity have not been fully clarified. W...

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Autores principales: Magno, Silvia, Ceccarini, Giovanni, Barison, Andrea, Fabiani, Iacopo, Giacomina, Alessandro, Gilio, Donatella, Pelosini, Caterina, Rubegni, Anna, Emdin, Michele, Gatti, Gian Luca, Santorelli, Filippo Maria, Sessa, Maria Rita, Santini, Ferruccio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963176/
https://www.ncbi.nlm.nih.gov/pubmed/33803191
http://dx.doi.org/10.3390/jcm10051142
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author Magno, Silvia
Ceccarini, Giovanni
Barison, Andrea
Fabiani, Iacopo
Giacomina, Alessandro
Gilio, Donatella
Pelosini, Caterina
Rubegni, Anna
Emdin, Michele
Gatti, Gian Luca
Santorelli, Filippo Maria
Sessa, Maria Rita
Santini, Ferruccio
author_facet Magno, Silvia
Ceccarini, Giovanni
Barison, Andrea
Fabiani, Iacopo
Giacomina, Alessandro
Gilio, Donatella
Pelosini, Caterina
Rubegni, Anna
Emdin, Michele
Gatti, Gian Luca
Santorelli, Filippo Maria
Sessa, Maria Rita
Santini, Ferruccio
author_sort Magno, Silvia
collection PubMed
description Laminopathies are disorders caused by LMNA gene mutations, which selectively affect different tissues and organ systems, and present with heterogeneous clinical and pathological traits. The molecular mechanisms behind these clinical differences and tissue specificity have not been fully clarified. We herein examine the case of a patient carrying a heterozygous LMNA c.1634G>A (p.R545H) variant with a mild, transient myopathy, who was referred to our center for the suspicion of lipodystrophy. At physical examination, an abnormal distribution of subcutaneous fat was noticed, with fat accumulation in the anterior regions of the neck, resembling the fat distribution pattern of familial partial lipodystrophy type 2 (FPLD2). The R545H missense variant has been found at very low allelic frequency in public databases, and in silico analysis showed that this amino acid substitution is predicted to have a damaging role. Other patients carrying the heterozygous LMNA p.R545H allele have shown a marked clinical heterogeneity in terms of phenotypic body fat distribution and severity of organ system involvement. These findings indicate that the LMNA p.R545H heterozygous variant exhibits incomplete penetrance and highly variable expressivity. We hypothesized that additional genetic factors, epigenetic mechanisms, or environmental triggers might explain the variable expressivity of phenotypes among various patients.
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spelling pubmed-79631762021-03-17 Partial Lipodystrophy and LMNA p.R545H Variant Magno, Silvia Ceccarini, Giovanni Barison, Andrea Fabiani, Iacopo Giacomina, Alessandro Gilio, Donatella Pelosini, Caterina Rubegni, Anna Emdin, Michele Gatti, Gian Luca Santorelli, Filippo Maria Sessa, Maria Rita Santini, Ferruccio J Clin Med Article Laminopathies are disorders caused by LMNA gene mutations, which selectively affect different tissues and organ systems, and present with heterogeneous clinical and pathological traits. The molecular mechanisms behind these clinical differences and tissue specificity have not been fully clarified. We herein examine the case of a patient carrying a heterozygous LMNA c.1634G>A (p.R545H) variant with a mild, transient myopathy, who was referred to our center for the suspicion of lipodystrophy. At physical examination, an abnormal distribution of subcutaneous fat was noticed, with fat accumulation in the anterior regions of the neck, resembling the fat distribution pattern of familial partial lipodystrophy type 2 (FPLD2). The R545H missense variant has been found at very low allelic frequency in public databases, and in silico analysis showed that this amino acid substitution is predicted to have a damaging role. Other patients carrying the heterozygous LMNA p.R545H allele have shown a marked clinical heterogeneity in terms of phenotypic body fat distribution and severity of organ system involvement. These findings indicate that the LMNA p.R545H heterozygous variant exhibits incomplete penetrance and highly variable expressivity. We hypothesized that additional genetic factors, epigenetic mechanisms, or environmental triggers might explain the variable expressivity of phenotypes among various patients. MDPI 2021-03-09 /pmc/articles/PMC7963176/ /pubmed/33803191 http://dx.doi.org/10.3390/jcm10051142 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Magno, Silvia
Ceccarini, Giovanni
Barison, Andrea
Fabiani, Iacopo
Giacomina, Alessandro
Gilio, Donatella
Pelosini, Caterina
Rubegni, Anna
Emdin, Michele
Gatti, Gian Luca
Santorelli, Filippo Maria
Sessa, Maria Rita
Santini, Ferruccio
Partial Lipodystrophy and LMNA p.R545H Variant
title Partial Lipodystrophy and LMNA p.R545H Variant
title_full Partial Lipodystrophy and LMNA p.R545H Variant
title_fullStr Partial Lipodystrophy and LMNA p.R545H Variant
title_full_unstemmed Partial Lipodystrophy and LMNA p.R545H Variant
title_short Partial Lipodystrophy and LMNA p.R545H Variant
title_sort partial lipodystrophy and lmna p.r545h variant
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963176/
https://www.ncbi.nlm.nih.gov/pubmed/33803191
http://dx.doi.org/10.3390/jcm10051142
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