{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T02:14:39Z","timestamp":1767838479522,"version":"3.49.0"},"reference-count":32,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["444748124"],"award-info":[{"award-number":["444748124"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>New techniques in molecular genetic diagnostics now allow for accurate diagnosis in a large proportion of patients with muscular diseases. Nevertheless, many patients remain unsolved, although the clinical history and\/or the muscle biopsy give a clear indication of the involved genes. In many cases, there is a strong suspicion that the cause must lie in unexplored gene areas, such as deep-intronic or other non-coding regions. In order to find these changes, next-generation sequencing (NGS) methods are constantly evolving, making it possible to sequence entire genomes to reveal these previously uninvestigated regions. Here, we present a young woman who was strongly suspected of having a so far genetically unsolved sarcoglycanopathy based on her clinical history and muscle biopsy. Using short read whole genome sequencing (WGS), a homozygous inversion on chromosome 13 involving SGCG and LINC00621 was detected. The breakpoint in intron 2 of SGCG led to the absence of \u03b3-sarcoglycan, resulting in the manifestation of autosomal recessive limb-girdle muscular dystrophy 5 (LGMDR5) in the young woman.<\/jats:p>","DOI":"10.3390\/genes13101752","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T20:58:47Z","timestamp":1664398727000},"page":"1752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Homozygous Inversion on Chromosome 13 Involving SGCG Detected by Short Read Whole Genome Sequencing in a Patient Suffering from Limb-Girdle Muscular Dystrophy"],"prefix":"10.3390","volume":"13","author":[{"given":"Natalie","family":"Pluta","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Biocenter, University of W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Hoffjan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederic","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Biocenter, University of W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Department of Neuropaediatrics, University Children\u2019s Hospital, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"L\u00fccke","sequence":"additional","affiliation":[{"name":"Department of Neuropaediatrics, University Children\u2019s Hospital, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Mohr","sequence":"additional","affiliation":[{"name":"Department of Neurology, Heimer Institute for Muscle Research, University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1782-4642","authenticated-orcid":false,"given":"Matthias","family":"Vorgerd","sequence":"additional","affiliation":[{"name":"Department of Neurology, Heimer Institute for Muscle Research, University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6139-788X","authenticated-orcid":false,"given":"Hoa Huu Phuc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7001-6644","authenticated-orcid":false,"given":"David","family":"Atlan","sequence":"additional","affiliation":[{"name":"Phenosystems SA, 1440 Braine le Chateau, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9307-7212","authenticated-orcid":false,"given":"Beat","family":"Wolf","sequence":"additional","affiliation":[{"name":"iCoSys, University of Applied Sciences Western Switzerland, 1700 Fribourg, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann-Kathrin","family":"Zaum","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Biocenter, University of W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Rost","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Biocenter, University of W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"},{"name":"Medical Genetics Center (MGZ), 80335 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/B978-0-08-045031-5.00003-7","article-title":"Sarcoglycanopathies","volume":"101","author":"Kirschner","year":"2011","journal-title":"Handb. Clin. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s004150070151","article-title":"Sarcoglycanopathies in Dutch patients with autosomal recessive limb girdle muscular dystrophy","volume":"247","author":"Ginjaar","year":"2000","journal-title":"J. Neurol."},{"key":"ref_3","first-page":"34667","article-title":"Assembly of the sarcoglycan complex","volume":"273","author":"Holt","year":"1998","journal-title":"Insights for muscular dystrophy. J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.nmd.2018.05.007","article-title":"229th ENMC International Workshop: Limb Girdle Muscular Dystrophies\u2014Nomenclature and Reformed Classification, Naarden, The Netherlands, 17\u201319 March 2017","volume":"28","author":"Straub","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_5","first-page":"1040","article-title":"Mild and severe muscular dystrophy caused by a single gamma-sarcoglycan mutation","volume":"59","author":"McNally","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1093\/brain\/awaa228","article-title":"New genotype-phenotype correlations in a large European cohort of patients with sarcoglycanopathy","volume":"143","author":"Bello","year":"2020","journal-title":"Brain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1097\/WCO.0000000000000371","article-title":"Next-generation sequencing approaches for the diagnosis of skeletal muscle disorders","volume":"29","author":"Nigro","year":"2016","journal-title":"Curr. Opin. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/S0140-6736(10)60599-5","article-title":"Challenges in the clinical application of whole-genome sequencing","volume":"375","author":"Ormond","year":"2010","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1136\/jmedgenet-2018-105272","article-title":"Whole-genome sequencing analysis of CNV using low-coverage and paired-end strategies is efficient and outperforms array-based CNV analysis","volume":"55","author":"Zhou","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/ng.2826","article-title":"Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis","volume":"46","author":"Weedon","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1093\/hmg\/dds055","article-title":"Whole-genome sequencing reveals a coding non-pathogenic variant tagging a non-coding pathogenic hexanucleotide repeat expansion in C9orf72 as cause of amyotrophic lateral sclerosis","volume":"21","author":"Herdewyn","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1136\/jmedgenet-2018-105778","article-title":"Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with developmental disorders","volume":"56","author":"Diguet","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/ng.3304","article-title":"Factors influencing success of clinical genome sequencing across a broad spectrum of disorders","volume":"47","author":"Taylor","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"403497","DOI":"10.1155\/2015\/403497","article-title":"DNAseq Workflow in a Diagnostic Context and an Example of a User Friendly Implementation","volume":"2015","author":"Wolf","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"D1207","DOI":"10.1093\/nar\/gkaa1043","article-title":"The Human Phenotype Ontology in 2021","volume":"49","author":"Kohler","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1093\/hmg\/4.4.615","article-title":"Inversion of the IDS gene resulting from recombination with IDS-related sequences is a common cause of the Hunter syndrome","volume":"4","author":"Bondeson","year":"1995","journal-title":"Hum. Mol. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/ng1193-236","article-title":"Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A","volume":"5","author":"Lakich","year":"1993","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00439-004-1118-6","article-title":"An intragenic deletion\/inversion event in the DMD gene determines a novel exon creation and results in a BMD phenotype","volume":"115","author":"Cagliani","year":"2004","journal-title":"Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/mus.22226","article-title":"Becker muscular dystrophy due to an inversion of exons 23 and 24 of the DMD gene","volume":"44","author":"Flanigan","year":"2011","journal-title":"Muscle Nerve"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/humu.20806","article-title":"Characterization of a complex Duchenne muscular dystrophy-causing dystrophin gene inversion and restoration of the reading frame by induced exon skipping","volume":"30","author":"Madden","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1002\/acn3.51201","article-title":"Long-read whole-genome sequencing for the genetic diagnosis of dystrophinopathies","volume":"7","author":"Xie","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1093\/bfgp\/elv020","article-title":"Human inversions and their functional consequences","volume":"14","author":"Puig","year":"2015","journal-title":"Brief. Funct. Genom."},{"key":"ref_24","first-page":"1779","article-title":"Identification of HMX1 target genes: A predictive promoter model approach","volume":"19","author":"Boulling","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lee, J., Han, K., Meyer, T.J., Kim, H.S., and Batzer, M.A. (2008). Chromosomal inversions between human and chimpanzee lineages caused by retrotransposons. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0004047"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"70","DOI":"10.5808\/GI.2016.14.3.70","article-title":"Structural Variation of Alu Element and Human Disease","volume":"14","author":"Kim","year":"2016","journal-title":"Genom. Inform."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1101\/gr.7.8.773","article-title":"Recombination hot spots and human disease","volume":"7","author":"Purandare","year":"1997","journal-title":"Genome Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nrm.2017.104","article-title":"The functions and unique features of long intergenic non-coding RNA","volume":"19","author":"Ransohoff","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Loda, A., and Heard, E. (2019). Xist RNA in action: Past, present, and future. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1008333"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.tig.2015.03.007","article-title":"The Landscape of long noncoding RNA classification","volume":"31","author":"Wahlestedt","year":"2015","journal-title":"Trends Genet."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zaum, A.K., Nanda, I., Kress, W., and Rost, S. (2022). Detection of pericentric inversion with breakpoint in DMD by whole genome sequencing. Mol. Genet. Genom. Med., e2028.","DOI":"10.1002\/mgg3.2028"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s10048-017-0531-7","article-title":"First large genomic inversion in familial cerebral cavernous malformation identified by whole genome sequencing","volume":"19","author":"Spiegler","year":"2018","journal-title":"Neurogenetics"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/10\/1752\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:41:02Z","timestamp":1760143262000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/10\/1752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,28]]},"references-count":32,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["genes13101752"],"URL":"https:\/\/doi.org\/10.3390\/genes13101752","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,28]]}}}