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. 2024 Feb;15(1):14-21.
doi: 10.1159/000533976. Epub 2023 Oct 16.

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

Gamze Sarıkaya Uzan  1 , Ceren Yılmaz Uzman  2 , Tayfun Çinleti  2 , Çağatay Günay  1 , Ayfer Ülgenalp  3 , Semra Hız Kurul  1 , Uluç Yiş  1
Affiliations

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

Gamze Sarıkaya Uzan et al. Mol Syndromol. 2024 Feb.

Abstract

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.

Keywords: Diagnostic yield; Limb-girdle muscular dystrophy; Neuromuscular disorders; Next-generation sequencing; Novel variant.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.
NGS panel results of the patients.
Fig. 2.
Fig. 2.
LGMD subtypes of the families.
Fig. 3.
Fig. 3.
Pedigree of the patients belonging to a shared familial lineage.
See this image and copyright information in PMC

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