Familial liver adenomatosis

2006-03-01   Jessica Zucman-Rossi 

Inserm U674, Génomique Fonctionnelle des tumeurs solides, 27 rue Juliette Dodu, 75010 Paris, France

Identity

Name

Familial liver adenomatosis

Alias

Familial hepatic adenomas

Note

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.

Inheritance

autosomal dominant disorder with low penetrance

Omim

142330

Orphanet

- -

Umls

-

Clinics

Phenotype and clinics

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.

Neoplastic risk

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

Evolution

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

Genes involved and Proteins

Note

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.

Alias

TCF1, LFB1, M57732, MODY3

Description

10 coding exons

Function

transcription factor

Homology

homeodomain, pou family

Germinal

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

Somatic

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

Bibliography

Pubmed IDLast YearTitleAuthors
145982632003Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation.Bacq Y et al
123550882002Bi-allelic inactivation of TCF1 in hepatic adenomas.Bluteau O et al
106361052000Liver adenomatosis: reappraisal, diagnosis, and surgical management: eight new cases and review of the literature.Chiche L et al
2079871978Familial liver-cell adenomas and diabetes mellitus.Foster JH et al
150016502004Hepatocyte nuclear factor-1 alpha gene inactivation: cosegregation between liver adenomatosis and diabetes phenotypes in two maturity-onset diabetes of the young (MODY)3 families.Reznik Y et al
89454701996Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3)Yamagata K et al
164963202006Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC.Zucman-Rossi J et al