Heterozygous deletion of FOXA2 segregates with disease in a family with heterotaxy, panhypopituitarism, and biliary atresia

Human Mutation
Ellen A TsaiNancy B Spinner

Abstract

Biliary atresia (BA) is a pediatric cholangiopathy with unknown etiology occurring in isolated and syndromic forms. Laterality defects affecting the cardiovascular and gastrointestinal systems are the most common features present in syndromic BA. Most cases are sporadic, although reports of familial cases have led to the hypothesis of genetic susceptibility in some patients. We identified a child with BA, malrotation, and interrupted inferior vena cava whose father presented with situs inversus, polysplenia, panhypopituitarism, and mildly dysmorphic facial features. Chromosomal microarray analysis demonstrated a 277 kb heterozygous deletion on chromosome 20, which included a single gene, FOXA2, in the proband and her father. This deletion was confirmed to be de novo in the father. The proband and her father share a common diagnosis of heterotaxy, but they also each presented with a variety of other issues. Further genetic screening revealed that the proband carried an additional protein-altering polymorphism (rs1904589; p.His165Arg) in the NODAL gene that is not present in the father, and this variant has been shown to decrease expression of the gene. As FOXA2 can be a regulator of NODAL expression, we propose that haploinsuffi...Continue Reading

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Citations

Dec 15, 2015·Journal of Pediatric Surgery·Mark Davenport
Apr 1, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jorge A BezerraRonald J Sokol
Jan 12, 2019·Molecular Genetics & Genomic Medicine·Karin Salehi KarlslättAgneta Nordenskjöld
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Nov 9, 2019·The Journal of Clinical Endocrinology and Metabolism·Louise Cheryl Gregory, Mehul Tulsidas Dattani
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Apr 23, 2020·International Journal of Molecular Medicine·Antonios KostourosJohn Tsiaoussis
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Sep 3, 2021·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Bixia ZhengFriedhelm Hildebrandt

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