{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:45:28Z","timestamp":1790178328901,"version":"4.1.0"},"reference-count":40,"publisher":"European Respiratory Society (ERS)","issue":"2","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publications.ersnet.org\/user-licence"}],"funder":[{"DOI":"10.13039\/100018232","name":"Orphan Disease Center, Perelman School of Medicine, University of Pennsylvania","doi-asserted-by":"publisher","award":["MDBR-23-019-NEHI"],"award-info":[{"award-number":["MDBR-23-019-NEHI"]}],"id":[{"id":"10.13039\/100018232","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2025,8,14]]},"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuroendocrine cell hyperplasia of infancy (NEHI), also called persistent tachypnoea of infancy (PTI), is a major cause of childhood interstitial lung disease. This rare lung disease is responsible for respiratory insufficiency in the first years of life. Non-pulmonary symptoms have also been reported, including failure to thrive and developmental delay. The pathophysiology of NEHI\/PTI remains unclear. To identify candidate genes of NEHI\/PTI, we performed whole-genome sequencing (WGS) and whole-exome sequencing (WES) in a large cohort of deeply phenotyped patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Trio WGS was performed (n=21) to identify a candidate gene. Following identification of a candidate gene, WES was performed to screen this gene in the remaining NEHI\/PTI patients (n=50).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four\n                      <jats:italic>de novo<\/jats:italic>\n                      loss-of-function (LoF) variants of\n                      <jats:italic>SRRM2<\/jats:italic>\n                      were identified in four out of 71 NEHI\/PTI patients with typical pulmonary presentation. Serine\/arginine repetitive matrix protein 2 (SRRM2) is involved in mRNA splicing, and\n                      <jats:italic>SRRM2<\/jats:italic>\n                      LoF variants have recently been reported in patients with neurodevelopmental delay (NDD). All four NEHI\/PTI patients also had mild NDD. The prevalence of\n                      <jats:italic>SRRM2<\/jats:italic>\n                      LoF variants in our cohort (5.6%, 95% CI 1.6\u201313.8%) is 20\u2013100 times higher than reported in patients with NDD without lung disease, therefore the phenotypic spectrum of\n                      <jats:italic>SRRM2-<\/jats:italic>\n                      associated disease should be extended to NEHI\/PTI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identifies\n                      <jats:italic>SRRM2-<\/jats:italic>\n                      related disorder as a monogenic cause of NEHI\/PTI. These results suggest that NEHI\/PTI patients should be evaluated by a paediatric neurologist and that\n                      <jats:italic>SRRM2<\/jats:italic>\n                      sequencing should be included in every NEHI\/PTI workup.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/13993003.00777-2025","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T15:15:45Z","timestamp":1758208545000},"page":"2500777","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["<i>D<\/i>\n                    <i>e novo SRRM2<\/i>\n                    variants in neuroendocrine cell hyperplasia of infancy and persistent tachypnoea of 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