Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype
Nemaline myopathy (NM) is a rare congenital myopathy characterised by hypotonia, muscle weakness, and often skeletal muscle deformities with the presence of nemaline bodies (rods) in the muscle biopsy. The nebulin (NEB) gene is the most commonly mutated and is thought to account for approximately 50...
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| Format: | Online |
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BioMed Central
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234932/ |
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pubmed-42349322014-11-19 Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype Malfatti, Edoardo Lehtokari, Vilma-Lotta Böhm, Johann De Winter, Josine M Schäffer, Ursula Estournet, Brigitte Quijano-Roy, Susana Monges, Soledad Lubieniecki, Fabiana Bellance, Remi Viou, Mai Thao Madelaine, Angéline Wu, Bin Taratuto, Ana Lía Eymard, Bruno Pelin, Katarina Fardeau, Michel Ottenheijm, Coen AC Wallgren-Pettersson, Carina Laporte, Jocelyn Romero, Norma B Research Nemaline myopathy (NM) is a rare congenital myopathy characterised by hypotonia, muscle weakness, and often skeletal muscle deformities with the presence of nemaline bodies (rods) in the muscle biopsy. The nebulin (NEB) gene is the most commonly mutated and is thought to account for approximately 50% of genetically diagnosed cases of NM. We undertook a detailed muscle morphological analysis of 14 NEB-mutated NM patients with different clinical forms to define muscle pathological patterns and correlate them with clinical course and genotype. Three groups were identified according to clinical severity. Group 1 (n = 5) comprises severe/lethal NM and biopsy in the first days of life. Group 2 (n = 4) includes intermediate NM and biopsy in infancy. Group 3 (n = 5) comprises typical/mild NM and biopsy in childhood or early adult life. Biopsies underwent histoenzymological, immunohistochemical and ultrastructural analysis. Fibre type distribution patterns, rod characteristics, distribution and localization were investigated. Contractile performance was studied in muscle fibre preparations isolated from seven muscle biopsies from each of the three groups. G1 showed significant myofibrillar dissociation and smallness with scattered globular rods in one third of fibres; there was no type 1 predominance. G2 presented milder sarcomeric dissociation, dispersed or clustered nemaline bodies, and type 1 predominance/uniformity. In contrast, G3 had well-delimited clusters of subsarcolemmal elongated rods and type 1 uniformity without sarcomeric alterations. In accordance with the clinical and morphological data, functional studies revealed markedly low forces in muscle bundles from G1 and a better contractile performance in muscle bundles from biopsies of patients from G2, and G3. BioMed Central 2014-04-12 /pmc/articles/PMC4234932/ /pubmed/24725366 http://dx.doi.org/10.1186/2051-5960-2-44 Text en Copyright © 2014 Malfatti et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Malfatti, Edoardo Lehtokari, Vilma-Lotta Böhm, Johann De Winter, Josine M Schäffer, Ursula Estournet, Brigitte Quijano-Roy, Susana Monges, Soledad Lubieniecki, Fabiana Bellance, Remi Viou, Mai Thao Madelaine, Angéline Wu, Bin Taratuto, Ana Lía Eymard, Bruno Pelin, Katarina Fardeau, Michel Ottenheijm, Coen AC Wallgren-Pettersson, Carina Laporte, Jocelyn Romero, Norma B |
| spellingShingle |
Malfatti, Edoardo Lehtokari, Vilma-Lotta Böhm, Johann De Winter, Josine M Schäffer, Ursula Estournet, Brigitte Quijano-Roy, Susana Monges, Soledad Lubieniecki, Fabiana Bellance, Remi Viou, Mai Thao Madelaine, Angéline Wu, Bin Taratuto, Ana Lía Eymard, Bruno Pelin, Katarina Fardeau, Michel Ottenheijm, Coen AC Wallgren-Pettersson, Carina Laporte, Jocelyn Romero, Norma B Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype |
| author_facet |
Malfatti, Edoardo Lehtokari, Vilma-Lotta Böhm, Johann De Winter, Josine M Schäffer, Ursula Estournet, Brigitte Quijano-Roy, Susana Monges, Soledad Lubieniecki, Fabiana Bellance, Remi Viou, Mai Thao Madelaine, Angéline Wu, Bin Taratuto, Ana Lía Eymard, Bruno Pelin, Katarina Fardeau, Michel Ottenheijm, Coen AC Wallgren-Pettersson, Carina Laporte, Jocelyn Romero, Norma B |
| author_sort |
Malfatti, Edoardo |
| title |
Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype |
| title_short |
Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype |
| title_full |
Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype |
| title_fullStr |
Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype |
| title_full_unstemmed |
Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype |
| title_sort |
muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype |
| description |
Nemaline myopathy (NM) is a rare congenital myopathy characterised by hypotonia, muscle weakness, and often skeletal muscle deformities with the presence of nemaline bodies (rods) in the muscle biopsy. The nebulin (NEB) gene is the most commonly mutated and is thought to account for approximately 50% of genetically diagnosed cases of NM. We undertook a detailed muscle morphological analysis of 14 NEB-mutated NM patients with different clinical forms to define muscle pathological patterns and correlate them with clinical course and genotype. Three groups were identified according to clinical severity. Group 1 (n = 5) comprises severe/lethal NM and biopsy in the first days of life. Group 2 (n = 4) includes intermediate NM and biopsy in infancy. Group 3 (n = 5) comprises typical/mild NM and biopsy in childhood or early adult life. Biopsies underwent histoenzymological, immunohistochemical and ultrastructural analysis. Fibre type distribution patterns, rod characteristics, distribution and localization were investigated. Contractile performance was studied in muscle fibre preparations isolated from seven muscle biopsies from each of the three groups. G1 showed significant myofibrillar dissociation and smallness with scattered globular rods in one third of fibres; there was no type 1 predominance. G2 presented milder sarcomeric dissociation, dispersed or clustered nemaline bodies, and type 1 predominance/uniformity. In contrast, G3 had well-delimited clusters of subsarcolemmal elongated rods and type 1 uniformity without sarcomeric alterations. In accordance with the clinical and morphological data, functional studies revealed markedly low forces in muscle bundles from G1 and a better contractile performance in muscle bundles from biopsies of patients from G2, and G3. |
| publisher |
BioMed Central |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234932/ |
| _version_ |
1613157689763823616 |