{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:28:18Z","timestamp":1792787298301,"version":"4.5.0"},"reference-count":53,"publisher":"BMJ","issue":"6","funder":[{"name":"NIH","award":["R01AI143810"],"award-info":[{"award-number":["R01AI143810"]}]},{"DOI":"10.13039\/501100012331","name":"LEO Foundation","doi-asserted-by":"crossref","award":["LF-OC-22-000965"],"award-info":[{"award-number":["LF-OC-22-000965"]}],"id":[{"id":"10.13039\/501100012331","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2025,2,9]]},"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>SLC29A3-related syndromes (SLC29A3-RS) are characterised by severe and multiorgan involvement that has a severe impact on the quality of life of the affected persons and therefore merit further genetic and clinical research. We investigated the clinical and genetic aspects of patients with SLC29A3-RS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Six pathogenic variants of the\n                      <jats:italic>SLC29A3<\/jats:italic>\n                      gene were identified in eight families in the current study. RNA sequencing was used for evaluating\n                      <jats:italic>SLC29A3<\/jats:italic>\n                      variant gene expression and protein stability by molecular dynamics (MD) simulations. This study conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of cases across five electronic databases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Genetic analysis revealed six pathogenic variants of the\n                      <jats:italic>SLC29A3<\/jats:italic>\n                      gene in eight families; one variant was shared among three families, indicating a possible founder effect. The estimated most recent common ancestor for these patients lived approximately 8.5 generations ago. MD studies revealed structural instability in mutant proteins. RNA sequencing also demonstrated that the expression of SLC29A3 was downregulated while the expression of the immune markers CD68 and LYZ was upregulated. A systematic search of 197 patients of different ethnic backgrounds revealed that the following symptoms were frequent findings: hyperpigmentation, hypertrichosis, hearing loss, short stature and hepatomegaly. The age of onset of SLC29A3-RS was 5.53\u00b15.24 years with an IQR of 1.4\u20138.25 years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The characterisation of the founder variants and the genotype-phenotype correlations helps delineate the phenotype spectrum of SLC29A3-RS, which will facilitate the genetic counselling and screening of the high-risk population. Findings on\n                      <jats:italic>SLC29A3<\/jats:italic>\n                      variants show the way to proceed in the process of developing the diagnostic and therapeutic methods in the management of SLC29A3-RS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2024-110606","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T03:41:42Z","timestamp":1742528502000},"page":"369-380","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Clinicogenetic characterisation of SLC29A3-related syndromes: a case series, tracing ancestral variants and molecular dynamics simulation"],"prefix":"10.1136","volume":"62","author":[{"given":"Sajjad","family":"Biglari","sequence":"first","affiliation":[{"name":"Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Isfahan Province, 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