{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:52:49Z","timestamp":1791010369099,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":274,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Limb\u2010girdle muscular dystrophies (LGMD) are a genetically heterogeneous group of neuromuscular disorders characterized by overlapping clinical features, including progressive muscle weakness and wasting, elevated creatine kinase (CK) levels, and motor and skeletal abnormalities. Due to phenotypic overlap and variable severity, clinical diagnosis alone is often unreliable. Incorporation of genetic investigations to aid diagnosis\/differential diagnosis has accelerated the diagnostic process but remains largely limited to developed countries. Here, we employed genetic testing as a first\u2010tier approach to simplify the diagnostic journey in a resource\u2010limited setting, combined with preliminary functional analyses to identify the underlying genetic cause. Our cohort included 46 affected individuals (31 males, 15 females) from 29 families with a mean age of 23.59 \u00b1 11.87\u2009years and a mean age at onset of 14.8 \u00b1 9.2\u2009years. All individuals presented with progressive muscle weakness, elevated CK levels, movement difficulties, and gait abnormalities. Genetic testing identified pathogenic\/likely pathogenic variants in\n                    <jats:italic>CAPN3<\/jats:italic>\n                    (8 families)\n                    <jats:italic>, DYSF<\/jats:italic>\n                    (15 families),\n                    <jats:italic>LAMA2<\/jats:italic>\n                    (4 families), and\n                    <jats:italic>SGCA<\/jats:italic>\n                    (1 family), whereas a variant of uncertain significance was identified in\n                    <jats:italic>COL12A1<\/jats:italic>\n                    (1 family). Preliminary functional investigations in patient\u2010derived fibroblasts demonstrated that the COL12A1: p.(Val1051Leu) identified in Family 1 results in reduced mRNA and protein abundance. Overall, 25 unique variants were identified, including 17 novel variants. This study highlights the utility of integrating genetic and functional approaches to facilitate accurate diagnosis in low\u2010 and middle\u2010income settings.\n                  <\/jats:p>","DOI":"10.1155\/humu\/1321391","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:02:55Z","timestamp":1791007375000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Approach to Diagnosing Limb\u2010Girdle Muscular Dystrophies in Resource\u2010Limited Settings"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1538-2883","authenticated-orcid":false,"given":"Hammad","family":"Yousaf","sequence":"first","affiliation":[{"name":"Department of Biological and Biomedical Sciences The Aga Khan University  Karachi Sindh Pakistan  aku.edu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubaba 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aku.edu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5152-5154","authenticated-orcid":false,"given":"Hijab","family":"Zahra","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences The Aga Khan University  Karachi Sindh Pakistan  aku.edu"},{"name":"Department of Medicine II University Hospital W\u00fcrzburg  W\u00fcrzburg Germany  ukw.de"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghazala","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences The Aga Khan University  Karachi Sindh Pakistan  aku.edu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1584-616X","authenticated-orcid":false,"given":"Kinza","family":"Rubab","sequence":"additional","affiliation":[{"name":"University Institute of Biochemistry and Biotechnology PMAS-Arid Agriculture University  Rawalpindi Punjab Pakistan  uaar.edu.pk"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazaratullah","family":"Azakai","sequence":"additional","affiliation":[{"name":"National Institute of Rehabilitation Medicine (NIRM)  Islamabad Islamabad Capital Territory Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3289-3128","authenticated-orcid":false,"given":"Haq Nawaz","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine The Aga Khan University  Karachi Sindh Pakistan  aku.edu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qamar","family":"Mahmood","sequence":"additional","affiliation":[{"name":"Faculty of Rehabilitation and Allied Health Sciences Riphah International University  Islamabad Islamabad Capital Territory Pakistan  riphah.edu.pk"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmat","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences The Aga Khan University  Karachi Sindh Pakistan  aku.edu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal Ahmad","family":"Mian","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences The Aga Khan University  Karachi Sindh Pakistan  aku.edu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2389-3337","authenticated-orcid":false,"given":"Zafar","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Genetics Forensic and Microbiology University of Swat  Swat Khyber Pakhtunkhwa Pakistan  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