Molecular Screening for G6PD Gene Mutations in Children with Glucose-6-Phosphate Dehydrogenase Deficiency

Background: Glucose-6-phosphate dehydrogenase (G6PD)deficiency is a heterogeneous enzyme abnormality with ahigh frequency among people of African, Mediterranean andSoutheast Asian origins. In almost every group studied in theMiddle East, only three to four different G6PD mutationswere detected. Among these, the G6PD Mediterranean mutation(563C-VT) was by far the most common. Apart from thismutation, little is known about the genetic heterogeneity ofG6PD deficiency in Egypt.Aim: To screen for G6PD gene mutations in a group ofEgyptian children with G6PD-deficiency who were previouslyscreened for the Mediterranean (563C-^T) mutation.Methodology: This work was conducted on twenty-oneunrelated Egyptian children (17 males and 4 females) presentingwith G6PD deficiency previously screened for the G6PDMediterranean mutation (563C-»T). Carefully-preserved DNAof patients refrigerated at -20°C and DNA of 21 age-matchednormal subjects extracted from blood leukocytes by saltingouttechnique were screened for mutations in the G6PD gene by PCR-single strand conformation polymorphism (SSCP) analysisfollowed by DNA sequencing.Results: In addition to the G6PD Mediterranean mutation563C-VT previously identified by PCR-RFLP analysis in 6/21male patients (28.6%), a further of 2 different mutations;G6PD A- mutation and G6PD Chatham were observed in 2/21(9.5%) and 1/21 (4.8%) patients respectively. Twelve patients(57.1%) remained uncharacterized at the genetic level, anormal African G6PD A genotype was detected in one patientof them. Patients with G6PD Mediterranean mutation weremore susceptible to hemolysis than were patients with G6PDA- and G6PD Chatham mutations.Conclusion: The lower prevalence of G6PD Mediterraneanmutation in our patients and the finding of three differentmutations in a relatively small number of G6PD-deficientsubjects reflect the considerable genetic heterogeneity ofG6PD deficiency of the Egyptian population.