Dados do Trabalho

Título

Diagnostic yield of whole-exome sequencing and genetic panel in adult Brazilian patients with myopathy

Resumo

Background: Myopathies in adults have multiple etiologies, but a significant proportion of cases are due to genetic variants in more than 200 known genes. Whole-exome sequencing (WES) and genetic panels (GP) have been employed as a diagnostic test in this setting with variable success rates. Factors such as age, ethnic background and phenotypic characterization of patients seem to influence in both accuracy for myopathies. Herein, we investigated the diagnostic yield of WES and GP in a cohort of adult patients with myopathy coming from a population with mixed ethnic background (Brazil). Objective: to determine the accuracy of WES and commercial GP in a population of patients from a reference neuromuscular center with suspected genetic myopathy.
Methods: 106 patients attending a reference neuromuscular center were recruited. Diagnosis for all of them remained elusive after physical examination, muscle biopsy, electrophysiology and lab tests. WES was performed following standard procedures for 30 patients, while GP was performed for 76. We identified variants labeled as pathogenic or likely pathogenic following ACMG guidelines. Then, diagnostic yield of WES and GP were determined for the whole cohort and for subgroups defined according to the major phenotypes.
Results: Mean age of patients was 38 years and there were 43% men. Definite genetic diagnosis was found in 12 from 30 patients in WES group (40% accuracy), while 36 from 76 in the genetic panel group (47%), leading to a diagnostic yield of 45% in this cohort. Pathogenic variants were found at TRAPPC11, SCN4A, ACADS, COL6A2, SGCB, CAPN3, SGCB, POLG, TWNK, RYR1, TRIM32, TTN, EMD, SLC25A4, TPM3, DOK7, DMD, ANO5, CHRNE, GAA, ADSSL1, CLCN1, PYGM, PNPLA, HACD1, NEB, DPAGT1, MYH7, FKTN.
Conclusions: WES and GP are useful diagnostic test for adult patients with undefined myopathy. In this mixed ethnic background cohort, diagnostic yield was 45% and variants in multiple genes were identified.