VACTERL-like phenotypes

Gene: KYNU

Comment on list classification: Confirmed with the clinical team that there is now enough evidence to make this gene green.

Created: 5 Sep 2017, 9:53 a.m.

A homozygous missense variant in this gene has been reported in a boy with jaundice and vomiting, who had massive urinary excretion of xanthurenic acid, 3-hydroxykynurenine and kynurenine, known as xanthurenic aciduria or hydroxykynureninuria - PMID:17334708.

Created: 11 Aug 2017, 8:44 a.m.

Comment on list classification: Two unrelated cases are reported in a new publication PMID: 28792876. One case in a consanguineous Lenanese family was found to be homozygous for a stop codon, both parents were heterozygous, and unaffected siblings were either homozyous for the wildtype allele or heterozygous. The second case in an American family, was compound heterozygous for two stop codons - one from each parent. In vitro studies show the variants results in reduced enzyme activity within the NAD de novo synthesis pathway, and knockout mouse model embryos develop similar defects to the patients. Added the 'treatable' tag to indicate that naicin supplementation during gestation prevented the malformations in the null mice.

Created: 11 Aug 2017, 8:38 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hydroxykynureninuria (Disorders of histidine, tryptophan or lysine metabolism); ?Hydroxykynureninuria, 236800; multiple congenital malformations; VACTERL-like phenotype

Publications

• 27604308
• 17334708
• 28792876