Glucose-6-phosphate dehydrogenase Buenos Aires: A novel de novo missense mutation associated with severe enzyme deficiency

Objective: Glucose 6-phosphate dehydrogenase (G6PD) catalyzes the first committed steps in the pentose phosphate pathway: the generation of NADPH by this enzyme is essential for protection against oxidative stress. The human enzyme is in a dimer ↔ tetramer equilibrium and its stability depends on NADP+ concentration. Herein, we report a case of a symptomatic baby affected by severe deficiency of G6PD activity due to a novel de novo genetic mutation (g1465C>T) in the thirteenth exon of its gene. Methods: Clinical, biochemical and genetic evaluations of the affected baby and his mother were performed. Results: We found the g1465C>T novel mutation, in the thirteenth exon of G6PD gene (named “G6PD Buenos Aires variant”). This g1465C>T mutation produce a P489S substitution at protein level. The P489S mutation was absent in his mother, suggesting that G6PD Buenos Aires resulted from a de novo mutation. Conclusions: The absence of mosaicism in the baby’s DNA (from saliva and blood samples) suggests that a de novo mutation event may occur in the very early stages in embryogenesis or in the mother’s germ cell lines.