New massive parallel sequencing approach improves the genetic characterization of congenital myopathies

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Oliveira, J (Author) Other; Goncalves, A (Author) Other; Taipa, R (Author) Other; Melo Pires, M (Author) Other; Oliveira, ME (Author) Other; Costa, JL (Author) Other; Machado JC (Author) FMUP; Medeiros, E (Author) Other; Coelho, T (Author) Other; Santos, M (Author) Other; Santos, R (Author) Other; sousa, m (Author) ICBAS

Journal

Title: Journal of Human Genetics

Vol. 61

Pages: 497-505

ISSN: 1434-5161

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 12 Citations

Scopus - 14 Citations

Other information

Authenticus ID: P-00K-KWX

DOI: 10.1038/jhg.2016.2

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9