Comparison for functional aberration of G-6-PD deficiency variants with exon 10 mutations

Abstract

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is a common inherited enzyme deficiency in many parts of the world and there are many different variants described. Every G-6-PD deficiency variant has a unique underlying genetic defect, therefore it manifests specific properties. The single amino acid substitution in the globin chain is the commonest form of G-6-PD deficiency variant. Usually, the G-6-PD deficiency variant with the pathogenesis of a single amino acid substitution presents with only one aberration in secondary structure. Although many G-6-PD deficiency variants present similar structural abnormal points their functions sometimes are discordant. Here, the author performed a functional analysis on some alpha haemoglobinopathies using a novel bioinformatic tool, Polyphen. The mutations of five G-6-PD deficiency variants with exon 10 mutations, Guadalajara (386 Arg?Cys), Beverly Hills (387 Arg?His), Serres (361 Ala?Val), Iowa (385 Lys?Glu), and Clinic (405 Met?Ile) were selected for further study in this investigation. According to the in silico mutation study, the functional change in the G-6-PD deficiency variants with exon 10 mutations studied is variable. Here, it indicates that the functional aberration in the G-6-PD deficiency variant is based on complex pathogenesis. The identification of the structural aberration only in a G-6-PD deficiency variant is not sufficient and should be supplemented with a further functional analysis for a better insight in this topic.

Keywords:

• Functional
• G-6-PD deficiency variant
• aberration
• Polyphen