{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:58:18Z","timestamp":1790081898283,"version":"4.0.1"},"reference-count":57,"publisher":"BMJ","issue":"3","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2024,12,22]]},"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Genotype-phenotype correlations in <jats:italic>PURA<\/jats:italic>-related neurodevelopmental disorders (<jats:italic>PURA<\/jats:italic>-NDDs) remain unclear. This systematic review aimed to clarify these correlations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Searches of PubMed and Embase were conducted on 8 August 2024 to identify studies that had investigated genetically diagnosed <jats:italic>PURA-<\/jats:italic>NDDs (5q31.3 deletion syndrome and PURA syndrome). All types and languages of studies were included. Study quality was assessed using a 20-item criterion checklist. Genetic and clinical data were extracted from each article and genotype-phenotype correlations were explored.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Our analysis included 46 studies encompassing 230 patients with <jats:italic>PURA<\/jats:italic>-NDDs (5q31.3 deletion syndrome 18 (8%) and PURA syndrome 212 (92%)). Patients with 5q31.3 deletion syndrome exhibited more congenital defects (50% vs 12%, p&lt;0.0001), respiratory difficulties (94% vs 63%, p=0.013) and walking disability (94% vs 55%, p=0.0026) than patients with PURA syndrome. In PURA syndrome, protein-truncating (nonsense or frameshift) variants were associated with more speech deficits (93% vs 80%, p=0.014) than non-protein-truncating (missense or in-frame) variants. <jats:italic>PURA<\/jats:italic> variant location had no effect on congenital defect occurrence or neurodevelopmental outcome. Overall, respiratory difficulties, walking disability and speech deficits were more commonly observed in the following order: 5q31.3 deletion (94%, 94% and 100%, respectively), multiple PUR-repeat deletions (68%, 60% and 95%, respectively), single PUR-repeat deletion or alteration (61%, 53% and 85%, respectively), and deletion or alteration located outside PUR repeats (38%, 33% and 43%, respectively).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The clinical severity of <jats:italic>PURA<\/jats:italic>-NDDs appears to be associated with the deletion\/alteration size including PUR repeats rather than the location of <jats:italic>PURA<\/jats:italic> variants.<\/jats:p>\n               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