NAD deficiency due to environmental factors or gene-environment interactions causes congenital malformations and miscarriage in mice.

ABSTRACT: Causes for miscarriages and congenital malformations can be genetic, environmental, or a combination of both. Genetic variants, hypoxia, malnutrition, or other factors individually may not affect embryo development, however, they may do so collectively. Biallelic loss-of-function variants in HAAO or KYNU, two genes of the nicotinamide adenine dinucleotide (NAD) synthesis pathway, are causative of congenital malformation and miscarriage in humans and mice. The variants affect normal embryonic development by disrupting the synthesis of NAD, a key factor in multiple biological processes, from its dietary precursor tryptophan, resulting in NAD deficiency. This study demonstrates that congenital malformations caused by NAD deficiency can occur independent of genetic disruption of

SUBMITTER: Cuny H 

PROVIDER: S-EPMC7035598 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature