HFE gene mutations an Apulian population: allele frequencies.

Hereditary hemochromatosis (HH) is an autosomal recessive trait regarding iron metabolism frequently found in Caucasian populations. The C282Y mutation of the HFE gene, held responsible for HH, has been identified as the major genetic basis for the phenotypic expression of HH whereas two additional mutations of the HFE H63D and S65C gene appear to be associated with a milder form of HH. A high allele frequency of C282Y and H63D has been reported in Northern European populations. In Italy, the overall allele frequency was 0.5% for the C282Y mutation, 12.6% for the H63D mutation and 1.1% for the S65C mutation. In this study, we evaluated the allele frequency of the three principal HFE mutations (C282Y, H63D, S65C) together with eight additional mutations (V53M, H63H, Q127H, E168Q, E168stop, W169stop, V59M, Q238P) in 500 healthy Apulian subjects. No subject homozygous for the C282Y mutation was found while 3% of subjects were heterozygous for this mutation. Heterozygosity and homozygosity for the H63D mutation were 26 and 1%, respectively. Only five subjects were heterozygous for the S65C mutation. Overall, the allele frequency was 1.5% for C282Y, 14% for H63D, 0.5% for S65C and 0% for the other mutations. The transferrin saturation (TS) was significantly higher in subjects heterozygous for the H63D mutations with respect to subjects with a normal genotype, though all were within the normal range. No statistically significant difference in the allele frequency was noted in the Apulian population compared to that in Northern and Southern Italy.

Genotype and phenotype correlation in glucose-6-phosphate dehydrogenase deficiency.

BACKGROUND AND OBJECTIVES: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common erythrocytic enzymatic disorder in Italy and is characterized by wide clinical, biochemical and molecular variability. We studied the clinical and hematologic data from 54 G6PD-deficient, unrelated males from the Apulia region. DESIGN AND METHODS: Analyses for enzymatic activity, G6PD electrophoresis and molecular typing were performed on all subjects. Thirty-nine subjects (72.2%) showed a severe G6PD deficiency (<10% residual enzymatic activity) and 15 subjects (27.8%) a moderate deficiency (10--60% residual activity). RESULTS: The Mediterranean variant was found in 48.2% of cases, the Seattle variant in 33.3%, the A- variant in 7.45% and the Montalbano variant in 3.7%; the variant was not identified in four subjects. Thirty-two patients (59.2%) were asymptomatic; of these, 37.04% demonstrated acute hemolytic crises induced mainly by ingestion of fava beans and 3.7% had had neonatal jaundice. Acute hemolytic anemia was found in 53.8% of subjects with the Mediterranean variant, in 5.5% with the Seattle variant, in 100% with the A-variant and 0% with the Montalbano variant. INTERPRETATION AND CONCLUSIONS: Enzymatic activity was shown to be a poor predictive parameter of acute hemolytic crises and was not correlated with clinical features. Subjects with Mediterranean or A- variants had a more severe clinical phenotype which was not related to enzymatic activity. The Seattle, and probably the Montalbano, variant appears to have a milder clinical expression.