Neonatal cholestasis

Gene: UGT1A1

Comment when marking as ready: Sufficient cases reported associated with Crigler-Najjar syndrome type I

Created: 25 Jul 2018, 3:04 p.m.

Comment on mode of inheritance: Monoallelic inheritance is seen in the less severe Gilberts syndrome which is usually recognized in adolescence, but cases of the more severe Crigler-Najjar syndrome, type I affecting neonates follows a biallelic pattern of inheritance.

Created: 25 Jul 2018, 3:02 p.m.

Comment on list classification: 50 variants from several publications reported for Crigler-Najjar syndromes.

Created: 25 Jul 2018, 2:59 p.m.

Comment on phenotypes: Added phenotypes from Jane Hartley and OMIM

Created: 25 Jul 2018, 2:52 p.m.

Comment on publications: Added publication from OMIM describing variants found.

Created: 25 Jul 2018, 2:51 p.m.

In OMIM this gene is associated with Crigler-Najjar syndrome, type I, Crigler-Najjar syndrome, type II, Hyperbilirubinemia, familial transient neonatal and also with [Bilirubin, serum level of, QTL1] and [Gilbert syndrome]. In Crigler-Najjar syndrome, type I, jaundice is apparent at birth or in infancy and so is a relevant neonatal liver dysfunction which is covered by this panel. OMIM report that Kadakol et al. (2000)(PMID: 11013440) lists 50 genetic lesions causing Crigler-Najjar syndromes. They report that Gilbert syndrome is associated with structurally normal UGT1A1 encoding region, but a variant type of promoter upstream to the coding sequences. Genetic lesions in both CN-1 and CN-2 patients may be located in any of the five exons of the UGT1A1 gene. Mutations are homozygous or compound heterozygous. Confirmed association with CRIGLER-NAJJAR SYNDROME, TYPE I in Gene2Phenotype.

Created: 25 Jul 2018, 2:49 p.m.

Green List (high evidence)

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Gilberts syndrome; Crigler Najjar syndrome 1 and 2; unconjugated jaundice