Bellance, Remi

Böhm, Johann

De Winter, Josine M.

Estournet, Brigitte

Eymard, Bruno

Fardeau, Michel

Laporte, Jocelyn

Lehtokari, Vilma-Lotta

Lubieniecki, Fabiana

Madelaine, Angéline

Malfatti, Edoardo

Monges, Soledad

Ottenheijm, Coen AC

Pelin, Katarina

Quijano-Roy, Susana

Romero, Norma B.

Schäffer, Ursula

Taratuto, Ana Lía

Viou, Mai Thao

Wallgren-Pettersson, Carina

Wu, Bin

Acta Neuropathologica Communications

PubMed

Edoardo Malfatti

Vilma-Lotta Lehtokari

Johann Böhm

Josine M De Winter

Ursula Schäffer

Brigitte Estournet

Susana Quijano-Roy

Soledad Monges

Fabiana Lubieniecki

Remi Bellance

Mai Thao Viou

Angéline Madelaine

Bin Wu

Ana Lía Taratuto

Bruno Eymard

Katarina Pelin

Michel Fardeau

Coen AC Ottenheijm

Carina Wallgren-Pettersson

Jocelyn Laporte

Norma B Romero

Crossref

Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype

Helsingin yliopiston digitaalinen arkisto

Muscle histopathology in nebulin-related nemaline myopathy : ultrastrastructural findings correlated to disease severity and genotype

International audienceNemaline 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.In conclusion NEB-mutated NM patients present a wide spectrum of morphological features. It is difficult to establish firm genotype phenotype correlation. Interestingly, there was a correlation between clinical severity on the one hand and the degree of sarcomeric dissociation and contractility efficiency on the other. By contrast the percentage of fibres occupied by rods, as well as the quantity and the sub sarcolemmal position of rods, appears to inversely correlate with severity. Based on our observations, we propose myofibrillar dissociation and changes in contractility as an important cause of muscle weakness in NEB-mutated NM patients

de Winter, Josine

Viou, Mai, Thao

Taratuto, Ana, Lía

Ottenheijm, Coen

Romero, Norma

HAL UVSQ

Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype.

Muscle histopathology in nebulin-related nemaline myopathy : ultrastrastructural findings correlated to disease severity and genotype

Abstract

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Helsingin yliopiston digitaalinen arkisto

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