Table 4 Diagnostic yield of Limb Girdle Muscular Dystrophy (LGMD) diagnosis with different methods from 2017 to 2023 (Bevilacqua et al. 2020; Chakravorty et al. 2020; Cotta et al. 2017; Lorenzoni et al. 2023; Özyilmaz et al., 2019; Reddy et al., 2017; Winckler et al. 2022; Yu et al. 2017)
Year | Diagnostic yield | N | Method of investigation (reference) | LGMD genes (patients confirmed/ method); number of genes tested if panel or type of exam; n = number of LGMD patients tested; unsolved diagnosis |
|---|---|---|---|---|
2017 | 59.6% | 151 | Single gene molecular sequencing, multiplex PCR, and muscle biopsy (Cotta et al. 2017) | CAPN3 (24/ Sequencing), DYSF (29/ muscle biopsy immunohistochemistry), SGCA, SGCB, SGCD, SGCG (26/ Multiplex PCR, and muscle biopsy immunohistochemistry), FKRP (8/ Sequencing), TCAP (3/ Sequencing, and muscle biopsy immunohistochemistry); 8 genes tested; n = 3412 neuromuscular patients (47% with confirmed diagnosis), among which n = 151 LGMD patients (according to the recent classification); other adult proximal muscular dystrophies solved LMNA-related (3), and CAV3-related (3); solved adult muscular dystrophies 96/157 (61%); solved LGMD = 90/151 (59.6%) (confirmed diagnosis combined with myopathological findings); unsolved LGMD = 61 |
2017 | 68.3%(*) | 180 | Next generation sequencing and muscle biopsy (Yu et al., 2017) | CAPN3 (26), DYSF (52), SGCA (8), FKRP (3), SGCB (1), SGCD (1), TRIM32 (1), POMT1 (1), ANO5 (1), n = 94 LGMD; Neuromuscular disease panel of 420 genes; 180 LGMD suspected patients submitted to Targeted next-generation sequencing; solved = 123/180 (68.3%) (confirmed diagnosis combined with myopathological findings); unsolved = 57 |
2017 | 40%(*) | 55 | Exome sequencing (Reddy et al., 2017) | ANO5 (3), COL6A3 (3), COL6A1 (1) CAPN3 (2), SGCG (2), SGCA (1), LAMA2 (1), and other neuromuscular non-LGMD diagnosis (9); exome; 55 LGMD families undiagnosed by traditional methods; total solved n = 22/55 (40%); unsolved = 33; LGMD solved = 13/55 (23.6%) |
2019 | 33.8%(*) | 74 | Next generation sequencing (Özyilmaz et al., 2019) | SGCA (6), CAPN3 (5), DYSF (5), SGCB (2), FKRP (2), POMT1 (1), SGCD (1), SGCG (1), LAMA2 (1); variants of unknown significance COL6A2 (3), TTN (1), PLEC (1), DAG1 (2); other myopathies (LMNA, FLNC); Next generation sequencing panel of 31 LGMD-associated genes; solved = 25/74 (33.8%); unsolved = 49 |
2020 | 49.0%(*) | 207 | Exome sequencing using an Agilent V5Plus exome capture kit to identify disease causative variants. Sequencing with Illumina HiSeq 2500 sequencing system with 100-basepair (bp) paired-end reads (Chakravorty et al. 2020) | ANO5 (3), CAPN3 (19), DNAJB6 (1), DYSF (27), LAMA2 (1), POMT1 (1), SGCA, SGCB, SGCD, SGCG (5), TCAP (2); exome; n = 207; LGMD solved = 59/207; other neuromuscular diseases solved = 42, among which GNE (31); total neuromuscular solved n = 101/207(49%); unsolved = 106 |
2020 | 55.8%(**) | 2103 | Next Generation Sequencing 10 gene-panel (Bevilacqua et al. 2020) | ANO5 (20), CAPN3 (90), DYSF (127), FKRP (18), GAA (9), SGCA (33), SGCB (10), SGCD (4), SGCG (9), TCAP (15); N = 2103; Total LGMD pathogenic variants = 335(16%); variants of unknown significance = 838(29.8%), solved(**) = 1173/2103(55.8%); unsolved = 930 |
2022 | 48.0% | 25 | Next Generation Sequencing (NGS) multi-gene panel (Winckler et al. 2022) | CAPN3 (5), DYSF (4), SGCA (1), TCAP (1). Other genes tested: COL6A1 (3) (congenital muscular dystrophy/ LGMD), ANO5, COL6A2, DNAJB6, FKRP, FKTN, LAMA2, POMGNT1, POMT1, POMT2, SGCB, SGCD, SGCG; 39 neuromuscular gene panel; total solved neuromuscular n = 31/51(60.8%); 17 LGMD genes tested; LGMD solved n = 12/25 (48%); unsolved LGMD = 13 |
2023 | 64.0% | 36 | 9-gene targeted next-generation sequencing panel, and muscle biopsy with immunohistochemistry (Lorenzoni et al. 2023) | CAPN3 (6), DYSF (6), TCAP (4), FKRP (3), SGCA/ SGCB/ SGCD/ SGCG (3), and ANO5 (1) 9 genes targeted next-generation sequencing panel (confirmed diagnosis combined with myopathological findings); solved LGMD = 23/36 (64%); unsolved = 23 |