Background: Approximately 180 mutations have been described in β-thalassemia worldwide with specific spectrum in each ethnic population. This study determines the spectrum and the frequency of β-thalassemia mutations in patients with β-thalassemia trait and sickle cell-β-thalassemia.Methods: Fifteen compound heterozygous sickle cell thalassemia (SCT) and 23 β-thalassemia trait patients were studied using reverse dot blot, denaturing gradient gel electrophoresis and direct genomic sequencing.Results: We detected distinct β-thalassemia alleles in 15 compound heterozygous of SCT and 23 β-thalassemia trait patients. The most common mutation was IVSII-1(G→A), found in 15 of the 38 thalassemia chromosomes. IVSII.1 (G→A) mutation is a single nucleotide change of G to A at intervening sequence 2 position 1 of β-globin gene, detected in 11 out of 23 chromosomes in A/β-thalassemic patients and in four out of 15 chromosomes of SCT patients. This mutation constituted about 39% of the mutations in both groups. The -25bp 3 IVSI, deletion of 25 base pairs from 3' end of intervening sequence 1 of β-globin gene, was found to be the second prevalent mutation among all chromosomes.Conclusion: Defining thalassemia mutations are necessary to establish prenatal diagnosis programs leading to lower medical cost. Amongst 10 different types of mutation detected in β- thalassemic patients from South of Iran, two mutations of IVSII-1(G→A) and -25bp 3' IVSI were the most predominant β-thalassemic alleles.    

Severe congenital neutropenia (SCN) is a rare primary immunodeficiency disease.Different genes are found to be associated with SCN, including ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3. The aim of this study was to find different gene mutations responsible for SCN in Iranian patients.Twenty-seven patients with SCN referred to Immunology, Asthma and Allergy Research Institute during a five year priod 5 years (May 2007 and May 2012), were included in this study. Neutropenia related exons and flanking regions of ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3 were amplified by PCR and the sequences were analyzed.The results showed different mutations including 4 ELANE mutations, 11 HAX1 mutations and 2 G6PC3 mutations. None of the patients had GFI1 mutation and also one mutation was found in G-CSFR in a patient with ELANE mutation. Ten patients had unknown genetic diagnosis which was compatible with other studies.According to these results, most of the patients showed HAX1 mutations and this finding which significantly differed from other reports, might be related to differences in Iranian ethnicity and also in high rate of consanguineous marriages in Iran.

Mitochondria contain their own DNA (mtDNA), which codes for 13 proteins (all subunits of the respiratory chain complexes), 22 tRNAs and 2 rRNAs. Several mtDNA point mutations as well as deletions have been shown to be causative in well-defined mitochondrial disorders. A mixture of mutated and wild type mtDNA (heteroplasmy) is found in most of these disorders. Inheritance of mtDNA is maternal, and mothers with heteroplasmic mtDNA transmit different proportions of normal and mutated mtDNA to the children. Mitochondrial tRNA genes have a central role in mitochondrial gene expression at the level of transcription, RNA processing and protein synthesis and they appear to be the mitochondrial genes most frequently affected by mutations causing diseases in man.