Neonatal cholestasis

Gene: HNF1B

Comment on mode of inheritance: There are no reports of biallelic variants in this gene in patients with cholestasis.

Created: 25 Jul 2018, 11 a.m.

Comment on list classification: Although this gene is not associated with cholestasis in OMIM or Gene2phenotype, 3 unrelated cases of cholestasis have been reported with SNVs in HNF1B (note HNF1B is within the common 17q12 microdeletion syndrome region, and some cases cited in 25741167 are associated with deletions rather than SNVs).

Created: 25 Jul 2018, 10:59 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cholestasis; renal cysts; diabetes; ciliopathy

Green List (high evidence)

PMID: 25741167 provides a review of the evidence of the role of HNF1B in neonatal and adult onset jaundice and cholestasis, in addition to the more widely known renal cysts and diabetes phenotype.

Has been seen in at least 7 unrelated patients with cholestasis arising at a wide range of ages. One child reported with non-hepatic biliary atresia as well as others with a paucity of intrahepatic bile ducts and some patients (later onset cholestasis) with what they designate a ciliopathy of cholangiocytes.

Mouse model of HNF1B demonstrates HNF1B important in development of biliary system, and knockouts have severe neonatal cholestasis. PMID: 11934849

Not currently listed as a phenotype of HNF1B in OMIM.

Created: 11 Jun 2018, 9:46 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• PMID: 25741167
• 11934849

Red List (low evidence)

This is a diabetes gene; we have not included it in our cholestasis panel becuase it doesnt have an OMIM entry associated to cholestasis or liver abnomral function.

Created: 4 Jun 2018, 11:33 a.m.

Phenotypes
diabetes mellitus; renal cysts and diabetes

Comment on list classification: Promoted to green, as there are more than 3 families reported with heterozygous variants in this gene for Renal cysts and diabetes syndrome.

Created: 22 May 2018, 2:10 p.m.