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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-7963176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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