Nemaline myopathies: a current view

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http://hdl.handle.net/10138/324648

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Sewry , C A , Laitila , J M & Wallgren-Pettersson , C 2019 , ' Nemaline myopathies: a current view ' , Journal of Muscle Research and Cell Motility , vol. 40 , no. 2 , pp. 111-126 . https://doi.org/10.1007/s10974-019-09519-9

Title: Nemaline myopathies: a current view
Author: Sewry, Caroline A.; Laitila, Jenni M.; Wallgren-Pettersson, Carina
Contributor: University of Helsinki, Katarina Pelin / Principal Investigator
University of Helsinki, Medicum
Date: 2019-06-21
Language: eng
Number of pages: 16
Belongs to series: Journal of Muscle Research and Cell Motility
ISSN: 1573-2657
URI: http://hdl.handle.net/10138/324648
Abstract: Nemaline myopathies are a heterogenous group of congenital myopathies caused by de novo, dominantly or recessively inherited mutations in at least twelve genes. The genes encoding skeletal α-actin (ACTA1) and nebulin (NEB) are the commonest genetic cause. Most patients have congenital onset characterized by muscle weakness and hypotonia, but the spectrum of clinical phenotypes is broad, ranging from severe neonatal presentations to onset of a milder disorder in childhood. Most patients with adult onset have an autoimmune-related myopathy with a progressive course. The wide application of massively parallel sequencing methods is increasing the number of known causative genes and broadening the range of clinical phenotypes. Nemaline myopathies are identified by the presence of structures that are rod-like or ovoid in shape with electron microscopy, and with light microscopy stain red with the modified Gömöri trichrome technique. These rods or nemaline bodies are derived from Z lines (also known as Z discs or Z disks) and have a similar lattice structure and protein content. Their shape in patients with mutations in KLHL40 and LMOD3 is distinctive and can be useful for diagnosis. The number and distribution of nemaline bodies varies between fibres and different muscles but does not correlate with severity or prognosis. Additional pathological features such as caps, cores and fibre type disproportion are associated with the same genes as those known to cause the presence of rods. Animal models are advancing the understanding of the effects of various mutations in different genes and paving the way for the development of therapies, which at present only manage symptoms and are aimed at maintaining muscle strength, joint mobility, ambulation, respiration and independence in the activities of daily living.
Subject: 3111 Biomedicine
Nemaline myopathy
Congenital myopathy
Rods
Rod bodies
Z line
Z disc
Animal models
GENOTYPE-PHENOTYPE CORRELATIONS
SKELETAL-MUSCLE
MOUSE MODEL
HYPERTROPHIC CARDIOMYOPATHY
INTRANUCLEAR RODS
FOUNDER MUTATION
BODY MYOPATHY
MICE LACKING
NEBULIN GENE
EXON 55
1182 Biochemistry, cell and molecular biology
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