Molecular Diagnosis of Limb-Girdle Muscular Dystrophy Using Next-Generation Sequencing Panels

Abstract

<b><i>Introduction:</i></b> Limb-girdle muscular dystrophies (LGMDs) are clinically and genetically heterogeneous muscle disorders. We aimed to share the diagnostic yield of an NGS gene panel containing LGMD-related genes and our experience with LGMD. <b><i>Methods:</i></b> Between February 2019 and October 2022, patients with a suspicion of LGMD and their relatives were reviewed in terms of demographic, clinical, and individual genetic data, age of symptom onset, sex, clinical features, LGMD types, cardiac involvement, muscle biopsy results, family history, and consanguinity. Our NGS gene panel consisted of <i>ANO5, CAPN3, CAV3, DAG1, DES, DNAJB6, DYSF, FKTN, FLNC, FRKP, GAA, GMPPB, HNRNPDL, ISPD, LIMS2, LMNA, MYOT, PLEC, POMGNT1, POMK, POMT1, POMT2, SGCA, SGCB, SGCD, SGCG, TCAP, TNPO3, TRAPPC11, TRIM32,</i> and <i>TTN</i> genes. <b><i>Results:</i></b> The diagnosis rate was 61.1% (11/18). Twelve (80%) patients with LGMD were male and three (20%) were female. The median age was 15.9 (range, 1.5–39) years. Our patient collective was drawn up out of patients with the following variants: LGMDR1 (<i>n</i> = 6; 40%), LGMDR2 (<i>n</i> = 4; 26.6%), LGMDR3 (<i>n</i> = 4; 26.6%), and LGMDR12 (<i>n</i> = 1; 6.7%). <b><i>Conclusion:</i></b> The present study showed that the NGS panel has a high success rate in the diagnosis of LGMD and contributes to early diagnosis.

Congenital LMNA-Related Muscular Dystrophy in Paediatrics: Cardiac Management in Monozygotic Twins

“…The adoption of personalised measures in both twins prevented malignant arrhythmias in the early stages of the disease, even though, unfortunately, both twins ultimately passed away. The clinical evolution was similar but delayed in one of the twins, suggesting that the cause of disease was the deleterious variant in the LMNA gene, identified using an NGS approach, in concordance with recent studies focused on the diagnosis of neuromuscular diseases [ 9 , 10 ]. However, other genetic alterations may modify the temporal onset/progression of phenotypic expression.…”