{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T01:08:38Z","timestamp":1781572118033,"version":"3.54.5"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,4,25]],"date-time":"2010-04-25T00:00:00Z","timestamp":1272153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Central congenital hypoventilation syndrome (CCHS) is an autonomous control disease producing hypoventilation, high PaCO<jats:sub>2<\/jats:sub>, and low PaO<jats:sub>2<\/jats:sub> during quiet sleep. The main gene variants detected in CCHS are mutations in the <jats:italic>PHOX2b<\/jats:italic> gene in up to 97% of isolated cases. However, CCHS is sometimes associated with autonomic diseases such as Hirschsprung disease (HSCR). Since genomic rearrangements in particularly sensitive areas of the <jats:italic>RET<\/jats:italic> protooncogene and\/or associated genes may account for the CCHS\/HSCR phenotype in patients without other detectable <jats:italic>RET<\/jats:italic> variants, the aim of the present study was to identify rearrangements in the coding sequence of <jats:italic>RET<\/jats:italic> as well as in three HSCR\u2010associated genes (<jats:italic>ZEB2<\/jats:italic>, <jats:italic>EDN3<\/jats:italic> and <jats:italic>GDNF<\/jats:italic>) in CCHS\/HSCR patients by using Multiplex Ligation\u2010dependent Probe Amplification (MLPA). We have screened 27 CCHS and 11 CCHS\/HSCR patients for genomic rearrangements in <jats:italic>RET, ZEB2, EDN3<\/jats:italic> and <jats:italic>GDNF<\/jats:italic> and did not identify any deletion or amplification in these four genes in all patients. We conclude that genomic rearrangements in <jats:italic>RET<\/jats:italic> are rare and were not responsible for the CCHS\/HSCR phenotype in individuals without identifiable germline <jats:italic>RET<\/jats:italic> variants in our group of patients, yet this possibility cannot be excluded altogether given the size of the cohort.<\/jats:p>","DOI":"10.1111\/j.1469-1809.2010.00577.x","type":"journal-article","created":{"date-parts":[[2010,4,26]],"date-time":"2010-04-26T00:58:10Z","timestamp":1272243490000},"page":"369-374","source":"Crossref","is-referenced-by-count":8,"title":["Analysis of <i>RET<\/i>, <i>ZEB2<\/i>, <i>EDN3<\/i> and <i>GDNF<\/i> Genomic Rearrangements in Central Congenital Hyperventilation Syndrome Patients by Multiplex Ligation\u2010dependent Probe Amplification"],"prefix":"10.1111","volume":"74","author":[{"given":"Alexandre","family":"Serra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"G\u00f6rgens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Alhadad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Fitze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans 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