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

Abstract

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 -α (rightward deletion) (45.6%), polyadenylation site (α°α) (α2) (AATAAA>AATGAA; HBA2: c.*92 A>G) (15.27%), - - (Mediterranean deletion) (6.86%), -α (leftward deletion), (6.17%), αα [Hb Constant Spring (Hb CS) (HBA2: c.427 T>C)] (4.62%), -α (HBA2: c.95+2_95+6delTGAGG) (3.70%). All chromosomes bearing an α-globin point mutation [α°α, -αα, αα, α°α (AATAAA> AATAAG; HBA2: c.*94 A>G)] showed only one haplotype that was present in most normal chromosomes, while the -α deletion was associated with three distinct haplotypes. Our results indicate that α-thal mutations are heterogeneous and -α and α°α are the most prevalent mutations in this region. The presence of -α with three different haplotypes suggests an older history for this mutation. The high prevalence of α°α 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).

First Report of Association Between Rare α-Thalassemia Mutation (HBA1: c.298A>T) and Hb Fontainebleau (HBA2: c.64G>C)

“…Alpha thalassemia is typically caused by deletions of HBA1 and HBA2 genes. Non-deletional mutations account for a small proportion of cases of a-thalassemia [2]. Approximately 220 a chain variants that showed variable phenotypes with regard to the position of the mutation have been detected around the world [8].…”

“…Hb Fontainebleau is a rare a 2 chain variant caused by an alanine to proline substitution at codon 21 [4,8], which has been previously reported in almost 24 cases around the world, four cases from Italy, two individuals from the UK, two from India and Iran, one from Cyprus, one from Iraq, and 12 cases from United Arab Emirates [3,4,7]. The a-globin mutations can affect mRNA processing, mRNA translation and globin chain stability [2]. Because the Iranian population is a mixture of different ethnic groups, frequency and distribution of a-globin mutations are different in various regions of this country.…”

Coinheritance of Sicilian (δβ)0-Thalassemia and Two Rare Hemoglobin Variants: A Complex Case of Hemoglobinopathy

“…Both alpha and beta thalassemia are frequent in Northern provinces of Iran, which harbors a very heterogeneous population [3]. Hb O-Indonesia, known as Hb Oliviere or Hb Buginese-X, has been reported in the Iranian, Italian, South African, Chinese, Makassar and Bugis of Sulawesi populations [4].…”

Prenatal diagnosis of thalassemia in 695 pedigrees from southeastern China: a 10‐year follow‐up study

“…The three common deletional α‐thalassemias were detected using a Gap‐PCR assay with the thalassemia gene detection kit (Shenzhen Yishengtang Biological Products Co., Ltd.; Shenzhen, China) according to the manufacturer's instructions, including ‐‐SEA , −α 3.7 and −α 4.2 mutations, 8 and 3 point mutations in α ‐ globin gene were identified using the polymerase chain reaction‐reverse dot blot hybridization (PCR‐RDB) assay with the thalassemia gene detection kit (Shenzhen Yishengtang Biological Products Co., Ltd.; Shenzhen, China) following the manufacturer's guidelines, including αQS, α CS , α QS , and α WS deletions 9 …”