{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T03:20:23Z","timestamp":1773976823047,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,4,19]],"date-time":"2017-04-19T00:00:00Z","timestamp":1492560000000},"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":[[2017,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>We evaluated a family with three siblings, two of whom ages 2 years and 19 months, had long segment colonic agangliosis and anisocoria. The mother also had anisocoria. All three affected family members were mildly dysmorphic with a flat facial profile, square appearance to the face, depressed nasal bridge, and anteverted nares. Genetic testing identified a novel heterozygous mutation, c.234C&gt;G, resulting in a premature stop codon in exon 1 of the <jats:italic>PHOX2B<\/jats:italic> gene. Screening for neural crest tumors was performed in the siblings and to date has been negative. This family supports a strong association between non polyalanine tract mutations, autonomic dysfunction, and Hirschsprung disease, but suggests mutation outside of the polyalanine tract may not dictate severe phenotype with significant respiratory compromise. A unique finding in this family is the association of congenital heart disease in two of the affected patients. These malformations may be a sporadic isolated finding or the result of environmental factors or a modifying allele. Given the association between congenital heart disease and aberrant neural crest cell development, however, findings are suggestive that congenital heart disease may be a rare feature of <jats:italic>PHOX2B<\/jats:italic> mutation which has not been previously reported.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38218","type":"journal-article","created":{"date-parts":[[2017,4,19]],"date-time":"2017-04-19T12:20:51Z","timestamp":1492604451000},"page":"1705-1709","source":"Crossref","is-referenced-by-count":14,"title":["Variable phenotype in a novel mutation in <i>PHOX2B<\/i>"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4810-4779","authenticated-orcid":false,"given":"Rachel C.","family":"Lombardo","sequence":"first","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital and Medical Center Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Kramer","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine Cincinnati Children's Hospital and Medical Center Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James F.","family":"Cnota","sequence":"additional","affiliation":[{"name":"Division of Cardiology Cincinnati Children's Hospital and Medical Center Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hemant","family":"Sawnani","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine Cincinnati Children's Hospital and Medical Center Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Hopkin","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital and Medical Center Cincinnati 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