title: Primary hepatocellular neoplasms in a MODY3 family with a novel HNF1A germline mutation.
abstract: Maturity onset diabetes of the young type 3 (MODY3) and hepatocellular adenomas (HCAs) are associated with mutations in the HNF1A gene. HNF1A codes for the transcription factor HNF1α, which interacts with DNA as a homodimer or a heterodimer with HNF1β, to regulate multiple cellular functions including glucidic metabolism, lipidic transport, and detoxication. We report three members of one family with a novel germline in-frame deletion of HNF1A exons 2-3 identified initially using array CGH and direct sequence analysis. All three family members have MODY3 in association with primary liver cell tumours (HCA, liver adenomatosis (LA), and hepatocellular carcinoma (HCC)). Additionally, a high rate of infant mortality was observed in the family. The described family demonstrates a novel HNF1A mutation associated with both benign and malignant primary liver cell tumours and MODY3.
authors.affiliation: Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: J S B
authors.initials: JS
authors.lastname: Willson
authors.forename: T D
authors.initials: TD
authors.lastname: Godwin
authors.forename: G A R
authors.initials: GA
authors.lastname: Wiggins
authors.forename: P J
authors.initials: PJ
authors.lastname: Guilford
authors.forename: J L
authors.initials: JL
authors.lastname: McCall
mesh_terms: D018248:Adenoma, Liver Cell / Q000150:complications* / Q000235:genetics*; D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics*; D005091:Exons; D005260:Female; D018095:Germ-Line Mutation; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D008113:Liver Neoplasms / Q000150:complications* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017384:Sequence Deletion
chemical_list: C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha
keywords: Diabetes; HNF1A; Hepatocellular adenoma; Hepatocellular carcinoma; MODY3