Distribution of β-Thalassemia Mutations in the Northern Provinces of Iran

Abstract

Beta-Thalassemia (thal) is one of the most common autosomal recessive disorders in Iran. There are more than two million carriers of beta-thal and over 15,000 people affected with beta-thal major who live in Iran. Prevalent mutations were identified by examining genomic DNAs isolated from 392 blood samples of beta-thal carriers from three northern provinces of Iran. Furthermore, 172 pregnant women were analyzed from the 196 couples who requested pregnant diagnosis for beta-thal. Allele identification was carried out using routine reverse dot-blot, amplification refractory mutation system (ARMS), and genomic sequencing. The most common mutation, IVS-II-1 (GA), is followed, in order of frequency, by codon 30 (GC), frameshift codons (FSC) 8,9 (+G), FSC 22/23/24 (-AAGTTGG), IVS-I-110 (GA), IVS-I-5 (GC), IVS-II-745 (CG), IVS-I-2 (TC), FSC 8 (-AA), IVS-I,3'-end (-25 bp), IVS-I-1 (GA), FSC 36/37 (-T), IVS-I-6 (TC), FSC 5 (-CT), -28 (AC), codon 37 (GA), IVS-II-2,3 (+11/-2), -30 (TA), and -88 (CA). We have also revealed the existence of five new mutations from northern Iran, one of which (codon 37) is the first reported for Iran. Furthermore, the rate of unknown mutations is significantly reduced in our study (about 6%). These results could help with establishing a center for prenatal diagnosis, prevention, and control of thalassemia in the northern provinces of Iran.

Simultaneous Detection of Hb Constant Spring (α142, TAA>CAA, α2) and The α2 IVS-I Donor Site (−TGAGG) Deletion by a Simple Polymerase Chain Reaction-Based Method in Iran

“…The α2 IVS-I donor site deletion is considered to be a Mediterranean mutation (3,9,15) and Hb CS rather as a Middle Eastern, Mediterranean and Southeast Asian one (3,6,(16)(17)(18). However, the relatively high prevalence of each mutation (12.2 and 8.8%, respectively), analyzed in nondeletional α-globin genes of mild anemic patients, confirms the heterogeneity of the studied population, also previously reported in βthal carriers (19,20). However, these prevalences may not reflect the real frequencies of these point mutations as all studied patients presented mild hypochromic and microcytic anemia, while many carriers of α + -thal can have normal MCV and MCH values.…”

Presence of the IVS-I-6-Mutated Allele in Beta-Thalassemia Major Patients Correlates with Extramedullary Hematopoiesis Incidence

“…The IVS-I-6 (T→C) mutation is one of the most common causes of β-thalassemia among individuals of Mediterranean and Middle Eastern ancestry [39,40]. Its high incidence has been reported among populations from Portugal [41]; Spain [42,43]; Albania [44]; the region of former Yugoslavia [45,46,47,48]; Greece [49,50,51,52]; Algeria [53]; Egypt [54]; Palestine [55,56]; Lebanon [57]; Syria [58,59]; Cyprus [60]; Turkey [61,62,63,64,65]; Saudi Arabia [66,67]; Iraq [68,69,70,71]; Iran [72,73,74]; and elsewhere. It results from a base substitution close to the 5′ splice junction, between exon I and intron I, and within a conserved consensus sequence, interfering with mRNA splicing and, consequently, reducing its efficiency.…”

Spectrum of α-Globin Gene Mutations in the Kerman Province of Iran

“…There are more than two million carriers of beta-thalassemia and over 25,000 people affected with beta-thalassemia major who live in Iran (5, 6). Previous studies show the most prevalent mutations in Iran are IVSI-5 (G> C), IVSII-I (G> A), Fr 8–9 (+G), and IVS-I-110 (G> A) (7).…”