{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:16:16Z","timestamp":1783016176201,"version":"3.54.6"},"reference-count":12,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Polyglucosan body myopathy type 2 (PGBM2; OMIM #616199) is an autosomal recessive myopathy caused by biallelic variants in\n                    <jats:italic>GYG1<\/jats:italic>\n                    , which encodes glycogenin\u20101. It is characterized by progressive muscle weakness and PAS\u2010positive, diastase\u2010resistant polyglucosan inclusions on muscle biopsy. We report a 64\u2010year\u2010old woman who developed progressive proximal weakness beginning in her early 50s, with polyglucosan bodies identified on muscle histopathology. Genome sequencing (GS) detected a single heterozygous pathogenic splice\u2010site variant, NM_004130.4(\n                    <jats:italic>GYG1<\/jats:italic>\n                    ):c.143+3G&gt;C. Given strong histopathologic evidence of PGBM2, GS data were reanalyzed, revealing an additional rare deep intronic variant, NM_004130.4(\n                    <jats:italic>GYG1<\/jats:italic>\n                    ):c.7+992T&gt;G, predicted to activate a cryptic exon. RNA sequencing (RNA\u2010seq) confirmed aberrant splicing from both variants, demonstrating exon 2 skipping associated with c.143+3G&gt;C and cryptic exon inclusion caused by c.7+992T&gt;G. Variant phasing posed a diagnostic challenge due to unavailable parental DNA, and long\u2010range PCR results were inconclusive. Long\u2010read GS definitively demonstrated that the two variants were in\n                    <jats:italic>trans<\/jats:italic>\n                    , establishing compound heterozygosity and confirming the molecular diagnosis. These findings enabled reclassification of the deep intronic variant as likely pathogenic. This case highlights the diagnostic limitations of conventional phasing approaches in adult\u2010onset recessive disorders and demonstrates the clinical utility of integrating genome reanalysis, RNA\u2010seq, and long\u2010read GS for resolving complex phasing challenges.\n                  <\/jats:p>","DOI":"10.1111\/cge.70173","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T09:03:49Z","timestamp":1776935029000},"page":"249-253","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unmasking Compound Heterozygosity in\n                    <scp>\n                      <i>GYG1<\/i>\n                    <\/scp>\n                    Myopathy: Diagnostic Insights From\n                    <scp>RNA<\/scp>\n                    \u2010Seq and Long\u2010Read Genomics"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2521-2937","authenticated-orcid":false,"given":"Deepak","family":"Panwar","sequence":"first","affiliation":[{"name":"Center for Individualized Medicine, Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7691-8334","authenticated-orcid":false,"given":"Joseph D.","family":"Farris","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine, Mayo Clinic  Rochester Minnesota USA"},{"name":"Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Mayo Clinic Functional Omics, Resource, Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J.","family":"Blake","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia W.","family":"Tan","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine, Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elie","family":"Naddaf","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic, Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9267-8705","authenticated-orcid":false,"given":"Joshua","family":"Sonnen","sequence":"additional","affiliation":[{"name":"Arkana Laboratories  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo Pinto e","family":"Vairo","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine, Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Medicine, Division of Gastroenterology and Hepatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J.","family":"Lambert","sequence":"additional","affiliation":[{"name":"Mayo Clinic Functional Omics, Resource, Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaas J.","family":"Wierenga","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics and Neurology Mayo Clinic  Jacksonville Florida USA"},{"name":"Department of Pediatric Genetics and Metabolism University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1009-6555","authenticated-orcid":false,"given":"Karthik","family":"Muthusamy","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics and Neurology Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric W.","family":"Klee","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine, Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Quantitative Health Sciences Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20111416"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24284"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2015.08.006"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9785-5"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2020.100597"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000208"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep21746"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010019\u20100217\u20109"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.10.004"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12995"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.06.002"}],"container-title":["Clinical 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