VACTERL-like phenotypesGene: HAAO
Comment on list classification: Confirmed with the clinical team that this gene has enough evidence to be green.
Created: 5 Sep 2017, 8:56 a.m.
Comment on list classification: 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: 11 Aug 2017, 9:02 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Multiple congenital malformations; VACTERL-like phenotype
This gene has been classified as Green List (High Evidence).
This gene has been classified as Amber List (Moderate Evidence).
HAAO was created by ellenmcdonagh
HAAO was added to VACTERL-like phenotypespanel. Sources: Literature