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Limb girdle muscular dystrophy due to LAMA2 gene mutations: new mutations expand the clinical spectrum of a still challenging diagnosis
Mutations in LAMA2 gene, encoding merosin, are generally responsible of a severe congenital-onset muscular dystrophy (CMD type 1A) characterized by severe weakness, merosin absence at muscle analysis and white matter alterations at brain Magnetic Resonance Imaging (MRI). Recently, LAMA2 mutations ha...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Pacini Editore Srl
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460730/ https://www.ncbi.nlm.nih.gov/pubmed/32904964 http://dx.doi.org/10.36185/2532-1900-009 |
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author | Magri, Francesca Brusa, Roberta Bello, Luca Peverelli, Lorenzo Del Bo, Roberto Govoni, Alessandra Cinnante, Claudia Colombo, Irene Fortunato, Francesco Tironi, Roberto Corti, Stefania Grimoldi, Nadia Sciacco, Monica Bresolin, Nereo Pegoraro, Elena Moggio, Maurizio Comi, Giacomo Pietro |
author_facet | Magri, Francesca Brusa, Roberta Bello, Luca Peverelli, Lorenzo Del Bo, Roberto Govoni, Alessandra Cinnante, Claudia Colombo, Irene Fortunato, Francesco Tironi, Roberto Corti, Stefania Grimoldi, Nadia Sciacco, Monica Bresolin, Nereo Pegoraro, Elena Moggio, Maurizio Comi, Giacomo Pietro |
author_sort | Magri, Francesca |
collection | PubMed |
description | Mutations in LAMA2 gene, encoding merosin, are generally responsible of a severe congenital-onset muscular dystrophy (CMD type 1A) characterized by severe weakness, merosin absence at muscle analysis and white matter alterations at brain Magnetic Resonance Imaging (MRI). Recently, LAMA2 mutations have been acknowledged as responsible of LGMD R23, despite only few cases with slowly progressive adult-onset and partial merosin deficiency have been reported. We describe 5 independent Italian subjects presenting with progressive limb girdle muscular weakness, brain white matter abnormalities, merosin deficiency and LAMA2 gene mutations. We detected 7 different mutations, 6 of which are new. All patients showed normal psicomotor development and slowly progressive weakness with onset spanning from childhood to forties. Creatin-kinase levels were moderately elevated. One patient showed dilated cardiomyopathy. Muscle MRI allowed to evaluate the degree and pattern of muscular involvement in all patients. Brain MRI was fundamental in order to address and/or support the molecular diagnosis, showing typical widespread white matter hyperintensity in T2-weighted sequences. Interestingly these alterations were associated with central nervous system involvement in 3 patients who presented epilepsy and migraine. Muscle biopsy commonly but not necessarily revealed dystrophic features. Western-blot was usually more accurate than immunohystochemical analysis in detecting merosin deficiency. The description of these cases further enlarges the clinical spectrum of LAMA2-related disorders. Moreover, it supports the inclusion of LGMD R23 in the new classification of LGMD. The central nervous system involvement was fundamental to address the diagnosis and should be always included in the diagnostic work-up of undiagnosed LGMD. |
format | Online Article Text |
id | pubmed-7460730 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Pacini Editore Srl |
record_format | MEDLINE/PubMed |
spelling | pubmed-74607302020-09-04 Limb girdle muscular dystrophy due to LAMA2 gene mutations: new mutations expand the clinical spectrum of a still challenging diagnosis Magri, Francesca Brusa, Roberta Bello, Luca Peverelli, Lorenzo Del Bo, Roberto Govoni, Alessandra Cinnante, Claudia Colombo, Irene Fortunato, Francesco Tironi, Roberto Corti, Stefania Grimoldi, Nadia Sciacco, Monica Bresolin, Nereo Pegoraro, Elena Moggio, Maurizio Comi, Giacomo Pietro Acta Myol Original Article Mutations in LAMA2 gene, encoding merosin, are generally responsible of a severe congenital-onset muscular dystrophy (CMD type 1A) characterized by severe weakness, merosin absence at muscle analysis and white matter alterations at brain Magnetic Resonance Imaging (MRI). Recently, LAMA2 mutations have been acknowledged as responsible of LGMD R23, despite only few cases with slowly progressive adult-onset and partial merosin deficiency have been reported. We describe 5 independent Italian subjects presenting with progressive limb girdle muscular weakness, brain white matter abnormalities, merosin deficiency and LAMA2 gene mutations. We detected 7 different mutations, 6 of which are new. All patients showed normal psicomotor development and slowly progressive weakness with onset spanning from childhood to forties. Creatin-kinase levels were moderately elevated. One patient showed dilated cardiomyopathy. Muscle MRI allowed to evaluate the degree and pattern of muscular involvement in all patients. Brain MRI was fundamental in order to address and/or support the molecular diagnosis, showing typical widespread white matter hyperintensity in T2-weighted sequences. Interestingly these alterations were associated with central nervous system involvement in 3 patients who presented epilepsy and migraine. Muscle biopsy commonly but not necessarily revealed dystrophic features. Western-blot was usually more accurate than immunohystochemical analysis in detecting merosin deficiency. The description of these cases further enlarges the clinical spectrum of LAMA2-related disorders. Moreover, it supports the inclusion of LGMD R23 in the new classification of LGMD. The central nervous system involvement was fundamental to address the diagnosis and should be always included in the diagnostic work-up of undiagnosed LGMD. Pacini Editore Srl 2020-06-01 /pmc/articles/PMC7460730/ /pubmed/32904964 http://dx.doi.org/10.36185/2532-1900-009 Text en ©2020 Gaetano Conte Academy - Mediterranean Society of Myology, Naples, Italy https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en This is an open access article distributed in accordance with the CC-BY-NC-ND (Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International) license. The article can be used by giving appropriate credit and mentioning the license, but only for non-commercial purposes and only in the original version. For further information: https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en |
spellingShingle | Original Article Magri, Francesca Brusa, Roberta Bello, Luca Peverelli, Lorenzo Del Bo, Roberto Govoni, Alessandra Cinnante, Claudia Colombo, Irene Fortunato, Francesco Tironi, Roberto Corti, Stefania Grimoldi, Nadia Sciacco, Monica Bresolin, Nereo Pegoraro, Elena Moggio, Maurizio Comi, Giacomo Pietro Limb girdle muscular dystrophy due to LAMA2 gene mutations: new mutations expand the clinical spectrum of a still challenging diagnosis |
title | Limb girdle muscular dystrophy due to LAMA2 gene mutations: new mutations expand the clinical spectrum of a still challenging diagnosis |
title_full | Limb girdle muscular dystrophy due to LAMA2 gene mutations: new mutations expand the clinical spectrum of a still challenging diagnosis |
title_fullStr | Limb girdle muscular dystrophy due to LAMA2 gene mutations: new mutations expand the clinical spectrum of a still challenging diagnosis |
title_full_unstemmed | Limb girdle muscular dystrophy due to LAMA2 gene mutations: new mutations expand the clinical spectrum of a still challenging diagnosis |
title_short | Limb girdle muscular dystrophy due to LAMA2 gene mutations: new mutations expand the clinical spectrum of a still challenging diagnosis |
title_sort | limb girdle muscular dystrophy due to lama2 gene mutations: new mutations expand the clinical spectrum of a still challenging diagnosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460730/ https://www.ncbi.nlm.nih.gov/pubmed/32904964 http://dx.doi.org/10.36185/2532-1900-009 |
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