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Neurological Sciences
Published in: Neurological Sciences 7/2022

17-02-2022 | Diseases of the neuromuscular synapses and muscles | Original Article

Diagnostic yield of multi-gene panel for muscular dystrophies and other hereditary myopathies

Authors: Pablo Brea Winckler, Bruna Cristine Chwal, Marco Antonnio Rocha Dos Santos, Daniela Burguêz, Marcia Polese-Bonatto, Edmar Zanoteli, Marina Siebert, Filippo Pinto e Vairo, Márcia Lorena Fagundes Chaves, Jonas Alex Morales Saute

Published in: Neurological Sciences | Issue 7/2022

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Abstract

Genetic testing is being considered the first-step in the investigation of hereditary myopathies. However, the performance of the different testing approaches is little known. The aims of the present study were to evaluate the diagnostic yield of a next-generation sequencing panel comprising 39 genes as the first-tier test for genetic myopathies diagnosis and to characterize clinical and molecular findings of families from southern Brazil. Fifty-one consecutive index cases with clinical suspicion of genetic myopathies were recruited from October 2014 to March 2018 in a cross-sectional study. The overall diagnostic yield of the next-generation sequencing panel was 52.9%, increasing to 60.8% when including cases with candidate variants. Multi-gene panel solved the diagnosis of 12/25 (48%) probands with limb-girdle muscular dystrophies, of 7/14 (50%) with congenital muscular diseases, and of 7/10 (70%) with muscular dystrophy with prominent joint contractures. The most frequent diagnosis for limb-girdle muscular dystrophies were LGMD2A/LGMD-R1-calpain3-related and LGMD2B/LGMD-R2-dysferlin-related; for congenital muscular diseases, RYR1-related-disorders; and for muscular dystrophy with prominent joint contractures, Emery-Dreifuss-muscular-dystrophy-type-1 and COL6A1-related-disorders. In summary, the customized next-generation sequencing panel when applied in the initial investigation of genetic myopathies results in high diagnostic yield, likely reducing patient’s diagnostic odyssey and providing important information for genetic counseling and participation in disease-specific clinical trials.
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Metadata
Title
Diagnostic yield of multi-gene panel for muscular dystrophies and other hereditary myopathies
Authors
Pablo Brea Winckler
Bruna Cristine Chwal
Marco Antonnio Rocha Dos Santos
Daniela Burguêz
Marcia Polese-Bonatto
Edmar Zanoteli
Marina Siebert
Filippo Pinto e Vairo
Márcia Lorena Fagundes Chaves
Jonas Alex Morales Saute
Publication date
17-02-2022
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 7/2022
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-022-05934-y

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