Molecular basis of G6PD deficiency

1. Molecular basis of G6PD deficiency Dr Narazah Mohd Yusoff Director, Human Genome Center, USM

2. Introduction G6PD deficiency � one of the most common inherited disorders, 400 million people affected �tropical and subtropical countries Epidemiological and in vitro studies - selection advantage during Plasmodium falciparum infection Most affected individuals asymptomatic, however risk of acute haemolysis

3. Genetics 1989 - more than 400 variants of G6PD Different biochemical forms of the enzyme exhibited, distinguished by different electrophoretic mobility, kinetic properties. Variants divided 5 classes according to the residual enzyme activity based (WHO). Mediterranean and African (A-) variants - by far the most clinically significant. Enzyme activity scarcely detectable in the Mediterranean type but close to normal in the African variant.

4. Genetics Thus, latter variant is considered to be the less severe form G6PD deficiency More recently, the dev.- new gene cloning techniques and complementary DNA sequencing techniques - identify the precise mutation of variants Many variants previously thought to be unique have proved to be identical.

5. Genetics Majority of the variants - from a single point-mutation resulting in amino acid substitution in gene encoding for G6PD located at the Xq28 region on the tip of the long arm of the X- chromosome.