A Comprehensive Molecular Investigation of α-Thalassemia in an Iranian Cohort from Different Provinces of North Iran.

α-Thalassemia (α-thal) is the most common monogenic disease that is caused by the absence or reduced expression of α-globin genes. The aim of this study was to investigate common α-globin mutations and their associated haplotypes in four northern provinces of Iran (Gilan, Mazandaran, Golestan, Khorasan). One thousand, one hundred and ninety-one persons were tested for α-thal mutations by gap-polymerase chain reaction (PCR), reverse dot-blot hybridization, restriction fragment length polymorphism (RFLP) analysis and sequencing. Of the nine different mutations found, the most frequent were -α3.7 (rightward deletion) (45.6%), polyadenylation site (αp°lyA2α) (α2) (AATAAA>AATGAA; HBA2: c.*92 A>G) (15.27%), - -MED (Mediterranean deletion) (6.86%), -α4.2 (leftward deletion), (6.17%), αCSα [Hb Constant Spring (Hb CS) (HBA2: c.427 T>C)] (4.62%), -α-5 nt (HBA2: c.95+2_95+6delTGAGG) (3.70%). All chromosomes bearing an α-globin point mutation [αp°lyA2α, -α-5 ntα, αCSα, αp°lyA1α (AATAAA> AATAAG; HBA2: c.*94 A>G)] showed only one haplotype that was present in most normal chromosomes, while the -α3.7 deletion was associated with three distinct haplotypes. Our results indicate that α-thal mutations are heterogeneous and -α3.7 and αp°lyA2α are the most prevalent mutations in this region. The presence of -α3.7 with three different haplotypes suggests an older history for this mutation. The high prevalence of αp°lyA2α in Mazandaran Province, Iran compared to other parts of the country and the world, suggests a founder effect. Altogether, we here provide further data confirming the heterogeneity of the northern population of Iran. These data may contribute to the establishment of a national mutation database, more accurate genetic counseling and prenatal diagnosis (PND).

Hematologic features of alpha thalassemia carriers.

Alpha thalassemia (α-thal) is relatively common worldwide. Most carriers are defective in either one or two alpha globin genes out of four functional ones, with deletions being more common than point mutations. The hematologic features are very important for the selection of the appropriate molecular tests while determining the genotype. The aim of this study was to compare hematologic features of patients with various types of α globin mutations. Hematological indices including red blood cells (RBC), hemoglobin concentration (Hb), mean cell volume (MCV), mean cell hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC) and percentage of Hemoglobin (HBA1, HBA2 and HBF) of seven-hundred and twenty two patients presenting ten different α-thal genotypes were considered. All patients showed reduced MCV and/or MCH values.Moreover, MCV and MCH were lower in patients with two functional alpha globin genes in comparison to patients with one mutated alpha globin gene (P value<0.001). In conclusion, MCV and MCH valuescan be helpful for the selection of the appropriate molecular tests to determine the genotype of alphathalassemia carriers.