Berk Özyilmaz1,2, Özgür Kirbiyik1, Taha R Özdemir1, Özge Kaya Özer1, Yaşar B Kutbay1, Kadri M Erdogan1, Merve Saka Güvenç1, Murat Yildirim Kale2, Hande Gazeteci3, Betül Kiliç4, Filiz Sertpoyraz2, Gulden Diniz5, Figen Baydan2, Pinar Gençpinar6, Nihal Olgaç Dündar6, Uluç Yiş7. 1. Genetic Diagnosis Center, Tepecik Training and Research Hospital, University of Health Sciences, Izmir, Turkey. 2. Neuromuscular Disorders Unit, Tepecik Training and Research Hospital, University of Health Sciences, Izmir, Turkey. 3. Pediatric Neurology, Cigli District Training Hospital, Izmir, Turkey. 4. Pediatric Neurology, Derince Education Research Hospital, Kocaeli, Turkey. 5. Department of Pathology, Izmir Democracy University, Izmir, Turkey. 6. Pediatric Neurology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Turkey. 7. Pediatric Neurology, School of Medicine, Dokuz Eylül University, Izmir, Turkey.
Abstract
INTRODUCTION: Limb-girdle muscular dystrophy (LGMD) is the fourth most common muscular dystrophy, with progressive proximal muscle weakness. However, a large number of neuromuscular conditions are similarly presented. Because of this, the use of high-throughput methods such as next-generation sequencing (NGS) is important in the evaluation of LGMD. METHODS: In this report, we applied a custom target capture-based NGS panel covering 31 LGMD-associated genes (MYOT, LMNA, CAV3, DES, DNAJB6, FLNC, CAPN3, DYSF, SGCG, SGCA, SGCB, SGCD, TCAP, TRIM32, FRKP, TTN, POMT1, ANO5, FKTN, POMT2, POMGnT1, DAG1, PLEC, GAA, GMPPB, HNRNPDL, TNPO3, LIMS2, POMK, TRAPPC11, ISPD) in 74 patients suspected of LGMD. RESULTS: In 25 (33.8%) out of 74 patients analyzed, one or more pathogenic/likely pathogenic variants in 13 different genes were detected. Six of the patients had the variants that were not found in databases and literature; thus, they were interpreted as novel pathogenic variants. DISCUSSION: The diagnosis rate achieved (33.8%) is consistent with previous literature reports and underlines the efficiency and importance of NGS technology in the molecular genetic evaluation of LGMD.
INTRODUCTION:Limb-girdle muscular dystrophy (LGMD) is the fourth most common muscular dystrophy, with progressive proximal muscle weakness. However, a large number of neuromuscular conditions are similarly presented. Because of this, the use of high-throughput methods such as next-generation sequencing (NGS) is important in the evaluation of LGMD. METHODS: In this report, we applied a custom target capture-based NGS panel covering 31 LGMD-associated genes (MYOT, LMNA, CAV3, DES, DNAJB6, FLNC, CAPN3, DYSF, SGCG, SGCA, SGCB, SGCD, TCAP, TRIM32, FRKP, TTN, POMT1, ANO5, FKTN, POMT2, POMGnT1, DAG1, PLEC, GAA, GMPPB, HNRNPDL, TNPO3, LIMS2, POMK, TRAPPC11, ISPD) in 74 patients suspected of LGMD. RESULTS: In 25 (33.8%) out of 74 patients analyzed, one or more pathogenic/likely pathogenic variants in 13 different genes were detected. Six of the patients had the variants that were not found in databases and literature; thus, they were interpreted as novel pathogenic variants. DISCUSSION: The diagnosis rate achieved (33.8%) is consistent with previous literature reports and underlines the efficiency and importance of NGS technology in the molecular genetic evaluation of LGMD.
Authors: Elisabeth A Kilroy; Amanda C Ignacz; Kaylee L Brann; Claire E Schaffer; Devon Varney; Sarah S Alrowaished; Kodey J Silknitter; Jordan N Miner; Ahmed Almaghasilah; Tashawna L Spellen; Alexandra D Lewis; Karissa Tilbury; Benjamin L King; Joshua B Kelley; Clarissa A Henry Journal: Elife Date: 2022-03-24 Impact factor: 8.140