{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:25:09Z","timestamp":1763036709619},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,7,20]],"date-time":"2012-07-20T00:00:00Z","timestamp":1342742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Congenital central hypoventilation syndrome (CCHS), a rare disorder characterized by alveolar hypoventilation and autonomic dysregulation, is caused by mutations in the <jats:italic>PHOX2B<\/jats:italic> gene. Most mutations occur de novo, but recent evidence suggests that up to 25% are inherited from asymptomatic parents with somatic mosaicism for these mutations. However, to date, germline mosaicism has not been reported. This report describes a family with recurrence of <jats:italic>PHOX2B<\/jats:italic> mutation\u2010confirmed CCHS due to germline mosaicism. The first occurrence was a baby girl, noted on day 2 of life to have multiple episodes of apnea, bradycardia, and cyanosis while breathing room air. <jats:italic>PHOX2B<\/jats:italic> gene testing confirmed the diagnosis of CCHS with a heterozygous polyalanine repeat expansion mutation (PARM); genotype 20\/27 (normal 20\/20). Both parents tested negative for this mutation using fragment analysis (limit of detection &lt;1%). Upon subsequent pregnancy [paternity confirmed using short tandem repeat (STR) analysis], amniocentesis testing identified the <jats:italic>PHOX2B<\/jats:italic> 20\/27 genotype, confirmed with repeat testing. Elective abortion was performed at 21.5 weeks gestation. Testing of abortus tissue confirmed amniocentesis testing. The <jats:italic>PHOX2B<\/jats:italic> 20\/27 expansion was not observed in a paternal sperm sample. This case represents the first reported family with recurrence of <jats:italic>PHOX2B<\/jats:italic> mutation\u2010confirmed CCHS without detection of a parental carrier state or mosaicism, confirming the previously hypothesized possibility of germline mosaicism for <jats:italic>PHOX2B<\/jats:italic> mutations. This is an important finding for genetic counseling of CCHS families, suggesting that even if somatic mosaicism is not detected in parental samples, there is still reason for careful genetic counseling and consideration of prenatal testing during subsequent pregnancies. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.35499","type":"journal-article","created":{"date-parts":[[2012,7,21]],"date-time":"2012-07-21T08:37:55Z","timestamp":1342859875000},"page":"2297-2301","source":"Crossref","is-referenced-by-count":22,"title":["Germline mosaicism of <i>PHOX2B<\/i> mutation accounts for familial recurrence of congenital central hypoventilation syndrome (CCHS)"],"prefix":"10.1002","volume":"158A","author":[{"given":"Casey M.","family":"Rand","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence J.","family":"Jennings","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelvin","family":"Panesar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M.","family":"Berry\u2010Kravis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra E.","family":"Weese\u2010Mayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,7,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1130"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-010-0718-y"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200602-305OC"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.33062"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.4.563"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3928\/0191-3913-19960501-11","article-title":"Congenital central hypoventilation syndrome: Ocular findings in 37 children","volume":"33","author":"Goldberg DS","year":"1996","journal-title":"J Pediatr Ophthalmol Strabismus"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1220941"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-1578(10)60598-3"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.21527"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/PDM.0b013e3181eb92ff"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1284"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.015412"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.128.4.2478"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9516"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/147.5.1185"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.151.6.864"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2008.01039.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-003-1036-z"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(93)90022-3"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019792"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(93)90006-V"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.1950200207"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(98)00073-5"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20040282"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200707-1079OC"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1086\/428366"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200807-1069ST"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20527"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1249"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)80901-1"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.35499","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.35499","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T07:00:35Z","timestamp":1697612435000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.35499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,20]]},"references-count":30,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2012,9]]}},"alternative-id":["10.1002\/ajmg.a.35499"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.35499","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,20]]}}}