Comment when marking as ready: As discussed in the GMS Gastrohepatology Specialist Test Group webex call 14th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.
Created: 31 Jan 2019, 10:42 a.m.
Initial gene list and info collated by Miranda Durkie Sheffield Diagnostic Genetics Service December 2018 on behalf of the GMS Gastrohepatology specialist test group. Gene Symbol submitted: UGT1A1; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Created: 7 Jan 2019, 4:42 p.m.
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.
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Gilberts syndrome; Crigler Najjar syndrome 1 and 2; unconjugated jaundice
Gene: ugt1a1 has been classified as Green List (High Evidence).
Source Other was added to UGT1A1. Mode of inheritance for gene UGT1A1 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes [Gilbert syndrome] 143500; Crigler-Najjar syndrome, type I 218800; Neonatal and Adult Cholestasis; Crigler-Najjar syndrome, type II 606785; unconjugated jaundice for gene: UGT1A1 Publications for gene UGT1A1 were changed from to 11013440
Source Expert Review Green was added to UGT1A1. Rating Changed from Red List (low evidence) to Green List (high evidence)
gene: UGT1A1 was added gene: UGT1A1 was added to Cholestasis. Sources: NHS GMS Mode of inheritance for gene: UGT1A1 was set to