{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T10:21:00Z","timestamp":1774606860484,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T00:00:00Z","timestamp":1555459200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatrics International"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital central hypoventilation syndrome (<jats:styled-content style=\"fixed-case\">CCHS<\/jats:styled-content>) is caused by mutation of paird\u2010like homeobox 2B (<jats:italic>PHOX2B<\/jats:italic>). Approximately 90% of patients were found to carry polyalanine repeat expansion mutation (<jats:styled-content style=\"fixed-case\">PARM<\/jats:styled-content>), and the remaining 10% had non\u2010<jats:styled-content style=\"fixed-case\">PARM<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">NPARM<\/jats:styled-content>). In <jats:styled-content style=\"fixed-case\">PARM<\/jats:styled-content>, the length of the polyalanine expansion correlates with clinical disease severity. Most patients with <jats:styled-content style=\"fixed-case\">NPARM<\/jats:styled-content> have hypoventilation symptoms in the neonatal period and complications of Hirschsprung disease, dysregulation of autonomic nervous system, and tumors of neural crest origin. Data on the genotype\u2013phenotype association may contribute to the clinical management of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied the genetic background of Japanese <jats:styled-content style=\"fixed-case\">CCHS<\/jats:styled-content> patients according to <jats:italic><jats:styled-content style=\"fixed-case\">PHOX<\/jats:styled-content>2B<\/jats:italic> sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 133 Japanese <jats:styled-content style=\"fixed-case\">CCHS<\/jats:styled-content> patients we identified 12 patients carrying 11 different <jats:styled-content style=\"fixed-case\">NPARM<\/jats:styled-content> (approx. 9% of the patients) and described the clinical manifestations in seven of them with the following novel mutations: c.941\u2010945del5, c.678_693dup16, c.609_616del8, c.620_633del14, c.663_711del 49, c.448C&gt;G and c.944G&gt;C. All patients had hypoventilation in the neonatal period and also had Hirschsprung disease, with the exception of two patients carrying c.620_633del14 and c.663_711del49 mutations. The patient carrying the c.609_616del8 mutation also had a benign mediastinal tumor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Most patients carrying <jats:styled-content style=\"fixed-case\">NPARM<\/jats:styled-content> had severe symptoms with frequent complications, as in previous reports, and should be carefully monitored for various complications, including neural crest\u2010derived tumor.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ped.13812","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T23:05:32Z","timestamp":1550703932000},"page":"393-396","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel <i><scp>PHOX<\/scp>2B<\/i> mutations in congenital central hypoventilation syndrome"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6609-0473","authenticated-orcid":false,"given":"Ayako","family":"Sasaki","sequence":"first","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine Yamagata City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumiko","family":"Kishikawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine Yamagata City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reisuke","family":"Imaji","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Hiroshima City Hiroshima Citizens Hospital Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Division of Neonatology Nagano Children's Hospital Azumino Nagano Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kyorin University Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Division of Neonatology Hiroshima City Hiroshima Citizens Hospital Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Division of Neonatology Saitama City Hospital Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichi","family":"Mino","sequence":"additional","affiliation":[{"name":"Division of Pediatrics and Perinatology Tottori University Faculty of Medicine Yonago Tottori Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuo","family":"Mitsui","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine Yamagata City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoshi","family":"Hayasaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine Yamagata City Japan"},{"name":"Department of Pediatrics Miyukikai Hospital Kaminoyama Yamagata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-197011000-00003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200807-1069ST"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.127.1.72"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.65"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1130"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-003-1036-z"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20527"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.015412"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.5664\/jcsm.3542","article-title":"A case of congenital central hypoventilation syndrome with a novel mutation of the PHOX2B gene presenting as central sleep apnea","volume":"10","author":"Amimoto Y","year":"2014","journal-title":"J. Clin. Sleep Med."},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200707-1079OC"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)01988-0"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0810-575"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23365"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/428366"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63401"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054043"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.053959"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1174-6"}],"container-title":["Pediatrics International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fped.13812","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ped.13812","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ped.13812","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1111%2Fped.13812","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ped.13812","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T16:33:55Z","timestamp":1694363635000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ped.13812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4]]},"references-count":20,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1111\/ped.13812"],"URL":"https:\/\/doi.org\/10.1111\/ped.13812","archive":["Portico"],"relation":{},"ISSN":["1328-8067","1442-200X"],"issn-type":[{"value":"1328-8067","type":"print"},{"value":"1442-200X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4]]},"assertion":[{"value":"2018-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}