New Massive Parallel Sequencing Approach Improves the Genetic Characterization of Congenital Myopathies

Overview

Journal J Hum Genet

Specialty Genetics

Date 2016 Feb 5

PMID 26841830

Citations 8

Authors

Jorge Oliveira

Ana Goncalves

Ricardo Taipa

Manuel Melo-Pires

Marcia E Oliveira

Jose Luis Costa

Jose Carlos Machado

Elmira Medeiros

Teresa Coelho

Manuela Santos

Rosario Santos

Mario Sousa

Affiliations

Soon will be listed here.

Abstract

Congenital myopathies (CMs) are a heterogeneous group of muscle diseases characterized by hypotonia, delayed motor skills and muscle weakness with onset during the first years of life. The diagnostic workup of CM is highly dependent on the interpretation of the muscle histology, where typical pathognomonic findings are suggestive of a CM but are not necessarily gene specific. Over 20 loci have been linked to these myopathies, including three exceptionally large genes (TTN, NEB and RYR1), which are a challenge for molecular diagnosis. We developed a new approach using massive parallel sequencing (MPS) technology to simultaneously analyze 20 genes linked to CMs. Assay design was based on the Ion AmpliSeq strategy and sequencing runs were performed on an Ion PGM system. A total of 12 patients were analyzed in this study. Among the 2534 variants detected, 14 pathogenic mutations were successfully identified in the DNM2, NEB, RYR1, SEPN1 and TTN genes. Most of these had not been documented and/or fully characterized, hereby contributing to expand the CM mutational spectrum. The utility of this approach was demonstrated by the identification of mutations in 70% of the patients included in this study, which is relevant for CMs especially considering its wide phenotypic and genetic heterogeneity.

Citing Articles

Nemaline myopathy: reclassification of previously reported variants according to ACMG guidelines, and report of novel genetic variants.

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Severe Neonatal RYR1 Myopathy With Pathological Features of Congenital Muscular Dystrophy.

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