Journal Article

Diagnostic yield of exome sequencing in myopathies: Experience of a Slovenian tertiary centre

Leonardis, Lea, Osredkar, Damjan, Peterlin, Borut, Meznaric, Marija, Babić Božović, Ivana, Maver, Aleš

2021

Overview

Our aim was to present the experience of systematic, routine use of next generation sequencing (NGS) in clinical diagnostics of myopathies. Exome sequencing was performed on patients with high risk for inherited myopathy, which were selected based on the history of the disease, family history, clinical presentation, and diagnostic workup. Exome target capture was performed, followed by sequencing on HiSeq 2500 or MiSeq platforms. Data analysis was performed using internally developed bioinformatic pipeline. The study comprised 86 patients, including 22 paediatric cases (26%). The largest group were patients referred with an unspecified myopathy (47%), due to non-specific or incomplete clinical and laboratory findings, followed by congenital myopathies (22%) and muscular dystrophies (22%), congenital myotonias (6%), and mitochondrial myopathies (3%). Altogether, a diagnostic yield was 52%; a high diagnostic rate was present in paediatric patients (64%), while in patients with unspecified myopathies the rate was 35%. We found 51 pathogenic/likely pathogenic variants in 23 genes and two pathogenic copy number variations. Our results provide evidence that phenotype driven exome analysis diagnostic approach facilitates the diagnostic rate of complex, heterogeneous disorders, such as myopathies, particularly in paediatric patients and patients with unspecified myopathies.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adolescent / Adult / Age / Aged / Biology and Life Sciences / Biomarkers - analysis / Biomarkers - metabolism / Biopsy / Cardiomyopathy / Child / Child, Preschool / Cognitive ability / Congenital diseases / Creatine / Creatine kinase / Data analysis / Diagnosis / Disease / Editing / Electromyography / Evaluation / Exome / Exome Sequencing - methods / Family medical history / Female / Follow-Up Studies / Genes / Genetic aspects / Genetic Testing - methods / Genetics / Genomes / Genomics / Genotype & phenotype / Health care facilities / Humans / Infant / Infant, Newborn / Kinases / Male / Medical diagnosis / Medical records / Medical tests / Medicine / Medicine and Health Sciences / Middle Aged / Muscle diseases / Muscles / Muscular Diseases - diagnosis / Muscular Diseases - epidemiology / Muscular Diseases - genetics / Muscular dystrophy / Mutation / Myopathy / Neurology / Neuromuscular diseases / Neurophysiology / Patients / Pediatrics / Phenotype / Prognosis / Research and Analysis Methods / Retrospective Studies / Signs and symptoms / Slovenia - epidemiology / Tertiary Care Centers - statistics & numerical data / Young Adult