Familial liver adenomatosis

Familial hepatic adenomas

Liver adenomatosis is a rare disease defined by the presence of multiple adenomas within an otherwise normal hepatic parenchyma. In 2002, frequent bi-allelic inactivation of TCF1\/HNF-1alpha, was identified in hepatocellular adenomas. In 80% of the cases both mutations were of somatic origin. However, in the remaining cases, one heterozygous germline mutation has been found in patients revealing a relation between liver adenomatosis and maturity-onset diabetes of the young (MODY3). MODY3 is a rare dominantly inherited subtype of non-insulin-dependent diabetes mellitus characterized by early onset, usually before the age of 25, and a primary defect in insulin secretion. In 1996, heterozygous germline mutations of TCF1\/HNF1a have been linked to the occurrence of MODY3 in humans.

autosomal dominant disorder with low penetrance

142330

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To date, all familial liver adenomatosis cases described are related to TCF1\/HFN1a constitutional mutation. Genotype-phenotype correlation analysis showed that TCF1\/HNF1a benign lesions were steatotic.

Among MODY3 patients only a very small minority will develop liver adenomatosis. Cases of malignant transformation are uncommon.

Patients presenting TCF1\/HNF1a mutated adenomatosis are at risk of tumor hemorrhagic rupture.

HNF1a is a homeodomain containing transcription factor that is implicated in hepatocyte differentiation and is required for the liver-specific expression of several genes, including β-fibrinogen, albumin and a1-antitrypsin.

TCF1, LFB1, M57732, MODY3

10 coding exons

transcription factor

homeodomain, pou family

at least 6 different mutations were found in familial adenomatosis: R229X, R272S, P291fs (2 cases), G55fs, IVS2 +1 G>T

inactivation of the second allele in adenoma tumors is by gene deletion or mutation.