title: GATA6 haploinsufficiency causes pancreatic agenesis in humans.
abstract: Understanding the regulation of pancreatic development is key for efforts to develop new regenerative therapeutic approaches for diabetes. Rare mutations in PDX1 and PTF1A can cause pancreatic agenesis, however, most instances of this disorder are of unknown origin. We report de novo heterozygous inactivating mutations in GATA6 in 15/27 (56%) individuals with pancreatic agenesis. These findings define the most common cause of human pancreatic agenesis and establish a key role for the transcription factor GATA6 in human pancreatic development.
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
authors.forename: Hana Lango
authors.initials: HL
authors.lastname: Allen
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flanagan
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Shaw-Smith
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
authors.forename: Elisa
authors.initials: E
authors.lastname: De Franco
authors.affiliation: Genomic Programming of Beta-cells Laboratory, Institut d'Investigacions August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.|Department of Endocrinology and Nutrition, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Ildem
authors.initials: I
authors.lastname: Akerman
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Caswell
authors.affiliation: Genomic Programming of Beta-cells Laboratory, Institut d'Investigacions August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.|Department of Endocrinology and Nutrition, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Ferrer
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
mesh_terms: D050993:GATA6 Transcription Factor / Q000235:genetics*; D057895:Haploinsufficiency; D006801:Humans; D010179:Pancreas / Q000002:abnormalities*; D010641:Phenotype
chemical_list: D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human