{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:12:07Z","timestamp":1761844327907},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,12,5]],"date-time":"2013-12-05T00:00:00Z","timestamp":1386201600000},"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":[[2014,2]]},"abstract":"<jats:sec><jats:label \/><jats:p>Recently, <jats:italic>GATA6<\/jats:italic> heterozygous loss\u2010of\u2010function mutations were reported to cause pancreatic agenesis and congenital heart defects (PACHD [OMIM:600001]). However, the molecular mechanisms resulting from premature termination codons have not been examined in this disorder. The objective of this study was to perform a genetic analysis of a patient with PACHD. A female patient presented with ventricular septal defect, patent ductus arteriosus, and congenital diaphragmatic hernia at birth. Permanent neonatal diabetes mellitus and pancreatic exocrine deficiency due to pancreatic agenesis was diagnosed at 1 month of age. PCR\u2010direct sequencing of <jats:italic>GATA6<\/jats:italic> revealed that the patient is heterozygous for a novel de novo nonsense mutation of c.1477C&gt;T, p. Arg493X in exon 5. RT\u2010PCR direct sequencing of the RT\u2010PCR products of total RNA from peripheral blood of the patient for the region encompassing exons 4\u20136 revealed only the wild\u2010type allele. This finding provides the evidence for the occurrence of nonsense\u2010mediated mRNA decay (NMD) in the p.Arg493X mutation. Quantitative RT\u2010PCR analysis revealed that the expression of <jats:italic>GATA6<\/jats:italic> transcript in the patient was less than half compared with normal control samples. This is the first evidence that <jats:italic>GATA6<\/jats:italic> haploinsufficiency is caused by NMD in vivo, and we conclude that <jats:italic>GATA6<\/jats:italic> haploinsufficiency causes not only PACHD but may affect other organs derived from the endoderm. Further screenings of <jats:italic>GATA6<\/jats:italic> mutations in patients with various forms of diabetes and\/or congenital heart disease with other visceral malformation may reveal the impact of <jats:italic>GATA6<\/jats:italic> mutations on diabetes and congenital malformation. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36275","type":"journal-article","created":{"date-parts":[[2013,12,5]],"date-time":"2013-12-05T20:27:03Z","timestamp":1386275223000},"page":"476-479","source":"Crossref","is-referenced-by-count":28,"title":["A case of pancreatic agenesis and congenital heart defects with a novel <i>GATA<\/i><i>6<\/i> nonsense mutation: Evidence of haploinsufficiency due to nonsense\u2010mediated mRNA decay"],"prefix":"10.1002","volume":"164","author":[{"given":"Shigeru","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Pediatrics Asahikawa Medical University Asahikawa 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