Genome sequencing with comprehensive variant calling identifies structural variants and repeat expansions in a large fraction of individuals with ataxia and/or neuromuscular disorders

• DOI: 10.3389/fneur.2023.1170005
• Publication Date: 2023-05-18T08:16:36Z
• Authors: Marlene Ek; Daniel Nilsson; Martin Engvall; Helena Malmgren; Håkan Thonberg; Maria Pettersson; Britt-Marie Anderlid; Anna Hammarsjö; Hafdis T. Helgado...; Snjolaug Arnardottir; Karin Naess; Inger Nennesmo; Martin Paucar; Helgi Thor Hjarta...; Rayomand Press; Göran Solders; Thomas Sejersen; Anna Lindstrand; Malin Kvarnung
• Keywords: Fraction (chemistry)

Introduction Neuromuscular disorders (NMDs) have a heterogeneous etiology. A genetic diagnosis is key to personalized healthcare and access targeted treatment for the affected individuals. Methods In this study, 861 patients with NMDs were analyzed genome sequencing comprehensive variant calling including single nucleotide variants, small insertions/deletions (SNVs/INDELs), structural variants (SVs) in panel of 895 NMD genes, as well short tandem repeat expansions (STRs) at 28 loci. addition, unsolved cases an unspecific clinical presentation, analysis OMIM disease genes was added. Results cohort, 27% (232/861) harbored pathogenic which STRs SVs accounted one-third (71/232). The found 107 different genes. Furthermore, 18 pediatric non-NMD Discussion Our results highlight that children hypotonia, genome-wide rather than disease-based gene should be considered diagnostic approach. More importantly, our clearly show it crucial include STR- SV-analyses diagnostics neuromuscular disorders.