Identification of a novel S184F mutation causing glucose-6-phosphate-dehydrogenase deficiency in a tribal family of Madhya Pradesh, Central India

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human erythroenzymopathy. G6PD deficiency in India is mainly due to the presence of the three common mutations namely, G6PD Orissa (131 C ➔ G), G6PD Mediterranean (563 C ➔ T) and G6PD Kerala Kalyan (949 G ➔ A). Here we report a novel G6PD mutation 551 C ➔ T in exon 6 with an amino acid change of Ser 184 Phe among the tribal groups of Madhya Pradesh (Central India) identified during a population screening programme. This enzyme variant has a severe erythrocyte G6PD deficiency and a fast electrophoretic mobility. Biochemical characterisation of this variant suggests a high Michaelis-Menton constant (Km) for glucose-6-phosphate (G6P) and decreased thermostability. Further, modelling based structural analysis suggests that despite low enzyme activity, substitution of phenylalanine with serine does not affect the functional properties of G6PD enzyme.