{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T01:46:26Z","timestamp":1766367986801,"version":"3.48.0"},"reference-count":40,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Gestational diabetes mellitus (GDM), the most common metabolic complication of pregnancy, is associated with a 50% increase in subsequent risk for type 2 diabetes. There is increasing interest in identifying biomarkers that may facilitate the stratification of subsequent type 2 diabetes risk among women with GDM. In this study, we considered the choline acetyltransferase (\n                      <jats:italic>ChAT<\/jats:italic>\n                      ) gene. CHAT plays a critical role in acetylcholine synthesis and regulates insulin secretion from the pancreatic islet to maintain glucose homeostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We screened for deleterious variants in the\n                      <jats:italic>ChAT<\/jats:italic>\n                      gene in 12 GDM patients and 10 ethnically matched controls from a South African cohort. We isolated DNA from the placental samples of these patients and performed DNA sequencing of the protein-coding region of the\n                      <jats:italic>ChAT<\/jats:italic>\n                      gene. Sequence alignments and variant annotations were done using UGENE software and Ensembl VEP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A novel heterozygous missense variant in exon 8 of the\n                      <jats:italic>ChAT<\/jats:italic>\n                      gene was identified. The plausible phenotypic impact of the variant\n                      <jats:italic>ChAT<\/jats:italic>\n                      (NM_020549.5):c.1213C&gt;G (p.Leu405Val) can be explained by haploinsufficiency, changing protein activities, strong transcription activity, and epigenetic repression activities of the variant. Also, structurally, the variant is located 18bp in-frame to a stop-gained variant (p.Gly411Ter). The RegulomeDB DNase expression data clearly show the identified variant in a peak expression in the spleen and placenta. This observation corroborates that the\n                      <jats:italic>ChAT<\/jats:italic>\n                      gene may play an essential role in GDM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Taken together, the metric scores for this variant show that it could affect the functions of the gene, but more functional studies are necessary to validate these effects. Consequently, this study sets the stage for the future screening of a larger cohort and functional validation of deleterious variants to underpin the\n                      <jats:italic>ChAT<\/jats:italic>\n                      gene and GDM association.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/med-2025-1225","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T15:58:30Z","timestamp":1752767910000},"source":"Crossref","is-referenced-by-count":0,"title":["The identification of novel missense variant in\n                    <i>ChAT<\/i>\n                    gene in a patient with gestational diabetes denotes plausible genetic association"],"prefix":"10.1515","volume":"20","author":[{"given":"Oluwafemi G.","family":"Oluwole","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town , PMB 7700, Observatory , Cape Town , South Africa"},{"name":"Biomedical Research Centre, Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford , Oxford , United Kingdom"},{"name":"Institute of Primate Research , Nairobi , Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afolake","family":"Arowolo","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council , Cape Town , South Africa"},{"name":"Department of Medicine, University of Cape Town , Cape Town , South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ezekiel","family":"Musa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kaduna State University , Kaduna , Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Levitt","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cape Town , Cape Town , South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mushi","family":"Matjila","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Cape Town , Cape Town , South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"doi-asserted-by":"crossref","unstructured":"Adam S, McIntyre HD, Tsoi KY, Kapur A, Ma RC, Dias S, et al. 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