CAKUT

Gene: HAAO

Comment on list classification: Confirmed with the clinical team that this gene has enough evidence to be green.

Created: 5 Sep 2017, 8:54 a.m.

Two unrelated cases are reported in a new publication PMID: 28792876. One case in a consanguineous Lenanese family (Family B) was found to be homozygous for a stop codon, both unaffected parents and 3 unaffected siblings were heterozygous. The second case in a consanguineous family from Iraq (Family A), was homozygous for a c.483dupT variants resulting in a stop codon. Both unaffected parents and 4 unaffected siblings were heterozygous. Metabolites upstream of HAAO in the kynurenine pathway were higher in patients A and B than unaffected family members. Downstream, levels of NAD+ in plasma from the patients were a third to a quarter the levels of unaffected family members. In vitro assays demonstrated that the stop codon variants result in reduced enzyme activity. Knockout mouse model embryos on a niacin-free diet developed similar defects to the patients. Added the 'treatable' tag to indicate that naicin supplementation during gestation prevented the malformations in the null mice.

Created: 14 Aug 2017, 12:11 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Multiple congenital malformations; VACTERL-like phenotype

Publications

• 27604308
• 17334708
• 28792876