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

• Published in: Molecular syndromology Vol. 15; no. 1; pp. 14 - 21
• Main Authors: Sarıkaya Uzan, Gamze, Yılmaz Uzman, Ceren, Çinleti, Tayfun, Günay, Çağatay, Ülgenalp, Ayfer, Hiz Kurul, Semra, Yiş, Uluç
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.02.2024
• Subjects: Original; Original Article; Novel variant; Diagnostic yield; Next-generation sequencing; Neuromuscular disorders; Limb-girdle muscular dystrophy
• ISSN: 1661-8769; 1661-8777
• DOI: 10.1159/000533976

Introduction: 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. Methods: 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 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, and TTN genes. Results: 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 (n = 6; 40%), LGMDR2 (n = 4; 26.6%), LGMDR3 (n = 4; 26.6%), and LGMDR12 (n = 1; 6.7%). Conclusion: The present study showed that the NGS panel has a high success rate in the diagnosis of LGMD and contributes to early diagnosis.