{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:07:19Z","timestamp":1785838039412,"version":"3.56.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    PGM2L1 is a crucial enzyme exhibiting glucose 1,6\u2010bisphosphate synthase activity, with predominant expression in brain tissue. In 2021, biallelic pathogenic variants in the\n                    <jats:italic>PGM2L1<\/jats:italic>\n                    gene were first linked to a neurodevelopmental disorder characterized primarily by developmental delay in four pediatric cases. In this study, we aimed to delineate the adult phenotype associated with the\n                    <jats:italic>PGM2L1<\/jats:italic>\n                    \u2010related neurodevelopmental disorder and to perform functional characterization of the identified variant. Two siblings presenting with neurodevelopmental delay were evaluated clinically and genetically. Exome sequencing of the older sibling revealed a homozygous nonsense variant, c.277C&gt;T p.(Gln73Ter), in the\n                    <jats:italic>PGM2L1<\/jats:italic>\n                    gene. This variant results in truncation leading to loss of key functional domains including the substrate binding site, catalytic active site, and protein stability regions. Quantitative analysis demonstrated a significant reduction in\n                    <jats:italic>PGM2L1<\/jats:italic>\n                    gene expression in both siblings compared to controls (\n                    <jats:italic>p<\/jats:italic>\n                    value\u2009&lt;\u20090.01). Unlike previously reported pediatric cases, the second sibling exhibited additional features including scoliosis, renal anomaly, tooth loss, hypothyroidism, bladder trabeculation, anhidrosis, and temperature intolerance, notably in the absence of obesity. These cases represent the first detailed description of an adult phenotype associated with a biallelic pathogenic variant in\n                    <jats:italic>PGM2L1<\/jats:italic>\n                    , expanding the clinical spectrum of this neurodevelopmental disorder.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64293","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T12:50:38Z","timestamp":1762174238000},"page":"673-684","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Delineating the Adult Phenotype of\n                    <scp>\n                      <i>PGM2L1<\/i>\n                    <\/scp>\n                    \u2010Related Neurodevelopmental Disorder"],"prefix":"10.1002","volume":"200","author":[{"given":"Pelin","family":"Ercoskun","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Basaksehir Cam and Sakura City Hospital  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7526-9835","authenticated-orcid":false,"given":"Ekrem","family":"Akbulut","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Malatya Turgut Ozal University  Malatya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1597-5922","authenticated-orcid":false,"given":"Cuneyd","family":"Yavas","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Biruni University  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lale","family":"Yilmaz Celik","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Basaksehir Cam and Sakura City Hospital  Istanbul 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