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

Abstract

Background Our aim was to present the experience of systematic, routine use of next generation sequencing (NGS) in clinical diagnostics of myopathies. Methods 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. Results 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. Conclusion 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.

Utility of exome sequencing for the diagnosis of pediatric-onset neuromuscular diseases beyond diagnostic yield: a narrative review

“…A study of NMD patients with mainly muscular affection was carried out by Božović et al WES test was performed in 22 pediatric patients evaluated for a variety of muscular diseases including DMD, CM, LGMD, and unspecified myopathy, reaching a notably high diagnostic yield of 64% [ 35 ].…”

Utilisation of Exome Sequencing for Muscular Disorders in Thai Paediatric Patients: Diagnostic Yield and Mutational Spectrum

“…7,8 Earlier research on ES in paediatric neuromuscular patients produced diagnostic yields ranging from 37-65%. [8][9][10][11] The high diagnostic rate for ES in the current investigation (70%) was probably due to several reasons. The patients referred to the 2 tertiary-care centres in this study were highly selective and strongly suspected to have genetic disorders.…”

Streamlined Two-Step Fragment Analysis PCR and Exome Sequencing of RFC1 for Diagnostic Testing of Suspected CANVAS Patients

“…Short-read Illumina exome sequencing was performed at the Clinical Insitute of Genomic Medicine, University Medical Centre Ljubljana, Slovenia (CIGM, UMCL), as previously described (Babić Božović et al, 2021). Variants in the RFC1 gene were classified according to the ACMG and AMP 2015 joint consensus recommendation (The ACMG Laboratory Quality Assurance Committee et al, 2015).…”