Clinical Features of LMNA-Related Cardiomyopathy in 18 Patients and Characterization of Two Novel Variants

Dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders characterized by ventricular dilation and depressed myocardial performance in the absence of hypertension, valvular, congenital, or ischemic heart disease. Mutations in LMNA gene, encoding for lamin A/C, account...

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Autores principales:	Valentina Ferradini, Joseph Cosma, Fabiana Romeo, Claudia De Masi, Michela Murdocca, Paola Spitalieri, Sara Mannucci, Giovanni Parlapiano, Francesca Di Lorenzo, Annamaria Martino, Francesco Fedele, Leonardo Calò, Giuseppe Novelli, Federica Sangiuolo, Ruggiero Mango
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	dilated cardiomyopathy (DCM) LMNA lamin A lamin C next generation sequencing (NGS) Medicine R
Acceso en línea:	https://doaj.org/article/cfa56b9959c84e2193cddbd219587381
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spelling	oai:doaj.org-article:cfa56b9959c84e2193cddbd2195873812021-11-11T17:41:53ZClinical Features of LMNA-Related Cardiomyopathy in 18 Patients and Characterization of Two Novel Variants10.3390/jcm102150752077-0383https://doaj.org/article/cfa56b9959c84e2193cddbd2195873812021-10-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/21/5075https://doaj.org/toc/2077-0383Dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders characterized by ventricular dilation and depressed myocardial performance in the absence of hypertension, valvular, congenital, or ischemic heart disease. Mutations in LMNA gene, encoding for lamin A/C, account for 10% of familial DCM. LMNA-related cardiomyopathies are characterized by heterogeneous clinical manifestations that vary from a predominantly structural heart disease, mainly mild-to-moderate left ventricular (LV) dilatation associated or not with conduction system abnormalities, to highly pro-arrhythmic profiles where sudden cardiac death (SCD) occurs as the first manifestation of disease in an apparently normal heart. In the present study, we select, among 77 DCM families referred to our center for genetic counselling and molecular screening, 15 patient heterozygotes for LMNA variants. Segregation analysis in the relatives evidences other eight heterozygous patients. A genotype–phenotype correlation has been performed for symptomatic subjects. Lastly, we perform in vitro functional characterization of two novel LMNA variants using dermal fibroblasts obtained from three heterozygous patients, evidencing significant differences in terms of lamin expression and nuclear morphology. Due to the high risk of SCD that characterizes patients with lamin A/C cardiomyopathy, genetic testing for LMNA gene variants is highly recommended when there is suspicion of laminopathy.Valentina FerradiniJoseph CosmaFabiana RomeoClaudia De MasiMichela MurdoccaPaola SpitalieriSara MannucciGiovanni ParlapianoFrancesca Di LorenzoAnnamaria MartinoFrancesco FedeleLeonardo CalòGiuseppe NovelliFederica SangiuoloRuggiero MangoMDPI AGarticledilated cardiomyopathy (DCM)LMNAlamin Alamin Cnext generation sequencing (NGS)MedicineRENJournal of Clinical Medicine, Vol 10, Iss 5075, p 5075 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dilated cardiomyopathy (DCM) LMNA lamin A lamin C next generation sequencing (NGS) Medicine R
spellingShingle	dilated cardiomyopathy (DCM) LMNA lamin A lamin C next generation sequencing (NGS) Medicine R Valentina Ferradini Joseph Cosma Fabiana Romeo Claudia De Masi Michela Murdocca Paola Spitalieri Sara Mannucci Giovanni Parlapiano Francesca Di Lorenzo Annamaria Martino Francesco Fedele Leonardo Calò Giuseppe Novelli Federica Sangiuolo Ruggiero Mango Clinical Features of LMNA-Related Cardiomyopathy in 18 Patients and Characterization of Two Novel Variants
description	Dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders characterized by ventricular dilation and depressed myocardial performance in the absence of hypertension, valvular, congenital, or ischemic heart disease. Mutations in LMNA gene, encoding for lamin A/C, account for 10% of familial DCM. LMNA-related cardiomyopathies are characterized by heterogeneous clinical manifestations that vary from a predominantly structural heart disease, mainly mild-to-moderate left ventricular (LV) dilatation associated or not with conduction system abnormalities, to highly pro-arrhythmic profiles where sudden cardiac death (SCD) occurs as the first manifestation of disease in an apparently normal heart. In the present study, we select, among 77 DCM families referred to our center for genetic counselling and molecular screening, 15 patient heterozygotes for LMNA variants. Segregation analysis in the relatives evidences other eight heterozygous patients. A genotype–phenotype correlation has been performed for symptomatic subjects. Lastly, we perform in vitro functional characterization of two novel LMNA variants using dermal fibroblasts obtained from three heterozygous patients, evidencing significant differences in terms of lamin expression and nuclear morphology. Due to the high risk of SCD that characterizes patients with lamin A/C cardiomyopathy, genetic testing for LMNA gene variants is highly recommended when there is suspicion of laminopathy.
format	article
author	Valentina Ferradini Joseph Cosma Fabiana Romeo Claudia De Masi Michela Murdocca Paola Spitalieri Sara Mannucci Giovanni Parlapiano Francesca Di Lorenzo Annamaria Martino Francesco Fedele Leonardo Calò Giuseppe Novelli Federica Sangiuolo Ruggiero Mango
author_facet	Valentina Ferradini Joseph Cosma Fabiana Romeo Claudia De Masi Michela Murdocca Paola Spitalieri Sara Mannucci Giovanni Parlapiano Francesca Di Lorenzo Annamaria Martino Francesco Fedele Leonardo Calò Giuseppe Novelli Federica Sangiuolo Ruggiero Mango
author_sort	Valentina Ferradini
title	Clinical Features of LMNA-Related Cardiomyopathy in 18 Patients and Characterization of Two Novel Variants
title_short	Clinical Features of LMNA-Related Cardiomyopathy in 18 Patients and Characterization of Two Novel Variants
title_full	Clinical Features of LMNA-Related Cardiomyopathy in 18 Patients and Characterization of Two Novel Variants
title_fullStr	Clinical Features of LMNA-Related Cardiomyopathy in 18 Patients and Characterization of Two Novel Variants
title_full_unstemmed	Clinical Features of LMNA-Related Cardiomyopathy in 18 Patients and Characterization of Two Novel Variants
title_sort	clinical features of lmna-related cardiomyopathy in 18 patients and characterization of two novel variants
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cfa56b9959c84e2193cddbd219587381
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Clinical Features of LMNA-Related Cardiomyopathy in 18 Patients and Characterization of Two Novel Variants

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