{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T03:34:57Z","timestamp":1768534497025,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,4,28]],"date-time":"2009-04-28T00:00:00Z","timestamp":1240876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2009,5]]},"abstract":"<jats:p>Congenital diaphragmatic hernia (CDH) is a common birth defect for which few causative genes have been identified. Several candidate regions containing genes necessary for normal diaphragm development have been identified, including a 4\u20135\u2003Mb deleted region at chromosome 1q41\u20101q42 from which the causative gene(s) has\/have not been cloned. We selected the <jats:italic>HLX <\/jats:italic>gene from this interval as a candidate gene for CDH, as the <jats:italic>Hlx <\/jats:italic>homozygous null mouse has been reported to have diaphragmatic defects and the gene was described as being expressed in the murine diaphragm. We re\u2010sequenced <jats:italic>HLX <\/jats:italic>in 119 CDH patients and identified four novel single nucleotide substitutions that predict amino acid changes: p.S12F, p.S18L, p.D173Y and p.A235V. These sequence alterations were all present in patients with isolated CDH, although patients with both isolated CHD and CDH with additional anomalies were studied. The single\u2010nucleotide substitutions were absent in more than 186 control chromosomes. <jats:italic>In\u2010situ <\/jats:italic>hybridization studies confirmed expression of <jats:italic>Hlx <\/jats:italic>in the developing murine diaphragm at the site of the junction of the diaphragm and the liver. Although functional studies to determine if these novel sequence variants altered the inductive activity of <jats:italic>Hlx <\/jats:italic>on the \u03b1\u2010smooth muscle actin and SM22\u03b1 promoters showed no significant differences between the variants and wild\u2010type <jats:italic>Hlx<\/jats:italic>, sequence variants in <jats:italic>HLX <\/jats:italic>may still be relevant in the pathogenesis of CDH in combination with additional genetic and environmental factors.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2009.01182.x","type":"journal-article","created":{"date-parts":[[2009,4,28]],"date-time":"2009-04-28T12:25:34Z","timestamp":1240921534000},"page":"429-439","source":"Crossref","is-referenced-by-count":30,"title":["Sequence variants in the <i>HLX <\/i>gene at chromosome 1q41\u20101q42 in patients with diaphragmatic 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