{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T12:55:04Z","timestamp":1793451304680,"version":"4.5.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Congenital central hypoventilation syndrome (CCHS), which is caused by <jats:italic>PHOX2B<\/jats:italic> with phenotypic variations, has a point of controversy: CCHS is putatively involved in autopsy cases of sudden unexpected infant death (SUID) including sudden infant death syndrome.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>The relation of CCHS to SUID cases was investigated by extensive genotyping of <jats:italic>PHOX2B<\/jats:italic>.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We analyzed 93 DNA samples of less than one-year-old SUID cases that were autopsied in our department. Unrelated adult volunteers (<jats:italic>n<\/jats:italic> = 942) were used as the control.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>No polyalanine tract expansion was detected in the SUID cases. The allelic frequencies of repeat contractions and SNP (rs28647582) in intron 2 were not significantly different from that in those control group. Further extensive sequencing revealed a non-polyalanine repeat mutation (NPARM) of c.905A&gt;C in a sudden death case of a one-month-old male infant. This missense mutation (p.Asn302Thr), registered as rs779068107, was annotated to \u2018Affected status is unknown\u2019, but it might be associated with the sudden death.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>NPARM was more plausibly related to sudden unexpected death than expansions because of severe clinical complications. This finding indicates possible CCHS involvement in forensic autopsy cases without ante-mortem diagnosis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0267751","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T17:32:23Z","timestamp":1651253543000},"page":"e0267751","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Non-polyalanine repeat mutation in PHOX2B is detected in autopsy cases of sudden unexpected infant death"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6596-4770","authenticated-orcid":true,"given":"Atsushi","family":"Ueda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0562-474X","authenticated-orcid":true,"given":"Motoki","family":"Osawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruaki","family":"Naito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Ochiai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6952-6292","authenticated-orcid":true,"given":"Yu","family":"Kakimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"key":"pone.0267751.ref001","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/ng1130","article-title":"Polyalanine 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Ventura","year":"2018","journal-title":"J Forensic Leg Med"},{"key":"pone.0267751.ref012","doi-asserted-by":"crossref","first-page":"642735","DOI":"10.3389\/fneur.2021.642735","article-title":"A common 3\u2019UTR variant of the PHOX2B gene is associated with infant life-threatening and sudden death events in the Italian population","volume":"12","author":"T Bachetti","year":"2021","journal-title":"Front Neurol"},{"key":"pone.0267751.ref013","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1007\/s00414-015-1213-3","article-title":"That\u2019s not it, either-neither polymorphisms in PHOX2B nor in MIF are involved in sudden infant death syndrome (SIDS)","volume":"129","author":"M Poetsch","year":"2015","journal-title":"Int J Legal Med"},{"key":"pone.0267751.ref014","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1212\/WNL.0000000000000781","article-title":"Genetic analysis of PHOX2B in sudden unexpected death in epilepsy cases","volume":"83","author":"RD 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