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In this study, we investigate the presence of\n                      <jats:italic>NARS2<\/jats:italic>\n                      variants in a large cohort of individuals with early\u2010onset diabetes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used genome and targeted next\u2010generation sequencing to screen for rare, coding biallelic\n                      <jats:italic>NARS2<\/jats:italic>\n                      variants in a cohort of 397 individuals diagnosed with diabetes &lt;24\u2009months of age of unknown genetic cause.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 8 individuals with homozygous disease\u2010causing missense variants in\n                      <jats:italic>NARS2<\/jats:italic>\n                      (4 individuals with the p.(Phe216Leu) variant, 3 with p.(Thr180Asn) and one with p.(Val440Leu)).\n                    <\/jats:p>\n                    <jats:p>\n                      All 8 individuals were diagnosed with insulin\u2010dependent diabetes before 6\u2009months of age (neonatal diabetes, NDM) with the median age at diagnosis being 4\u2009weeks (range: 1 to 20\u2009weeks). 7\/8 probands had low birthweight (median\n                      <jats:italic>Z<\/jats:italic>\n                      \u2010score: \u22122.43, range: \u22124.17 to 0.86). Neurological features were common, with epilepsy and developmental delay each identified in 7\/8 and 6\/8 participants, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Taken together with previously published cases, this study shows that NDM is an important feature of COXPD\u201024 and highlights a critical role for NARS2 in the insulin\u2010secreting pancreatic \u03b2\u2010cell.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dme.70129","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T02:06:44Z","timestamp":1756692404000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neonatal diabetes mellitus is a significant feature of\n                    <scp>COXPD<\/scp>\n                    \u201024 caused by recessive\n                    <scp>\n                      <i>NARS2<\/i>\n                    <\/scp>\n                    variants"],"prefix":"10.1111","volume":"42","author":[{"given":"Russell","family":"Donis","sequence":"first","affiliation":[{"name":"Department of Clinical and Biomedical Science University of Exeter Medical School  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew N.","family":"Wakeling","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Science University of Exeter Medical School  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Jeffery","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Science University of Exeter Medical School  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Govier","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Science University of 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