MOLECULAR HETEROGENEITY UNDERLYING THE G6PD MEDITERRANEAN PHENOTYPE

As part of a study aiming to define the molecular basis of glucose-6-p hosphate dehydrogenase (G6PD) deficiency, we analysed a sample from a Portugese boy with a family history of favism. Although the biochemica l properties of red-cell G6PD from this subject were similar to those of the common variant G6PD Mediterranean, the corresponding mutation ( 563 C --> T) was not present. Instead, polymerase chain reaction (PCR) amplification and sequencing of the entire gene detected a C --> T tr ansition at nucleotide 592 in exon VI, changing an arginine residue to a cysteine residue only 10 amino acids downstream from the Mediterran ean mutation. Single-strand conformation polymorphism analysis of a PC R-amplified DNA fragment spanning exons VI and VII of the G6PD gene ha s detected the same mutation, confirmed by sequencing, in a G6PD-defic ient patient from Southern Italy. We name this new variant G6PD Coimbr a.