Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation.

Abstract

BACKGROUND & AIMS:

Germline mutations in hepatocyte nuclear factor 1alpha (TCF1/HNF-1alpha) are associated with maturity-onset diabetes of the young type 3 (MODY3), and somatic biallelic inactivations of the gene are found in hepatocellular adenomas and liver adenomatosis. This study investigated cosegregation of HNF-1alpha germline mutations with diabetes and liver adenomatosis in 2 families.

METHODS:

Two unrelated patients with liver adenomatosis and harboring HNF-1alpha germline and somatic mutations were studied. Subsequently, we screened 9 relatives in the 2 independent families for diabetes, hepatocellular adenomas, and HNF-1alpha germline mutations.

RESULTS:

In family A, a father and his son presented with an intraperitoneal hemorrhagic rupture of a liver adenomatosis without diabetes. A heterozygous R229X germline mutation was identified in HNF-1alpha in the father and his son and also in his second 27-year-old son without hepatocellular adenomas. In family B, a diagnosis of liver adenomatosis was made fortuitously in a 14-year-old girl. A heterozygous G55fsX57 germline mutation in HNF-1alpha was identified in this patient, her diabetic father, and her 2 sisters. Systematic exploration showed liver adenomatosis in the 2 sisters. Somatic inactivation of the second HNF-1alpha allele was found in liver tumors in both families.

CONCLUSIONS:

This study describes familial liver adenomatosis and shows the association with germline HNF-1alpha mutations in adults and children. It also highlights the importance of screening for hepatocellular adenomas, diabetes, and HNF-1alpha germline mutations in relatives of patients with liver adenomatosis. Finally, prevalence of liver adenomatosis remains to be evaluated in MODY3 subjects.

• Authors: Yannick Bacq, Emmanuel Jacquemin, Charles Balabaud, Emmanuelle Jeannot, Beatrice Scotto, Sophie Branchereau, Christophe Laurent, Pascal Bourlier, Daniele Pariente, Anne de Muret, Monique Fabre, Paulette Bioulac-Sage, Jessica Zucman-Rossi
• Journal: Gastroenterology (Gastroenterology) Vol. 125 Issue 5 Pg. 1470-5 (Nov 2003) ISSN: 0016-5085 [Print] United States
• PMID: 14598263 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• HNF1A protein, human
• HNF1B protein, human
• Hepatocyte Nuclear Factor 1-alpha
• Nuclear Proteins
• Transcription Factors
• Hepatocyte Nuclear Factor 1
• Hepatocyte Nuclear Factor 1-beta

Topics

• Adenoma (diagnosis, genetics, pathology)
• Adolescent
• Adult
• DNA-Binding Proteins
• Female
• Gene Silencing
• Germ-Line Mutation
• Hepatocyte Nuclear Factor 1
• Hepatocyte Nuclear Factor 1-alpha
• Hepatocyte Nuclear Factor 1-beta
• Heterozygote
• Humans
• Liver Neoplasms (diagnosis, genetics, pathology)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Neoplastic Syndromes, Hereditary (diagnosis, genetics, pathology)
• Nuclear Proteins
• Pedigree
• Transcription Factors (genetics)