The Carrier Frequency of α-Globin Gene Triplication in an Iranian Population with Normal or Borderline Hematological Parameters

Abstract

The -α(3.7) rightward deletion is the most frequent α-globin mutation worldwide, while frequencies of the ααα(anti 3.7) triplication are only sporadically known. Carriers of the ααα(anti 3.7) triplication show no clinical symptoms or significant hematological changes, but co-inheritance with β-thalassemia (β-thal) has been reported to worsen the clinical and hematological features of the patient as well as the trait. We have screened the α-globin gene rearrangements of 280 individuals with normal hematological indices and 117 persons with borderline hematological parameters. We used multiplex polymerase chain reaction (m-PCR) and multiplex ligation-dependent probe amplification (MLPA) technology to detect triplications and quadruplications. Only the ααα(anti 3.7) triplication was observed. The carrier frequency in the first group was 2.14% and in the second group 1.7%. No phenotype aggravation was noticed in two carriers of β-thal and the ααα(anti 3.7) triplication, while a mild β-thalassemia intermedia (β-TI) was observed in a β-thal carrier with six α-globin genes. Due to the high consanguinity in the country, homozygosity for the ααα(anti 3.7) triplication and for other rearrangements can be expected. Therefore, an accurate determination of the frequencies and a routine control for these mutations is essential for a correct genotype-phenotype prediction during genetic counseling for β-thal.

Alpha-Thalassemia Mutations in Adana Province, Southern Turkey: Genotype-Phenotype Correlation

“…These results show that -a 3.7 gene deletion is prevalent worldwide including our country and indicate that our results are in agreement with literature. The -a 3.7 deletion is the most frequent a-globin mutation, while frequencies of the aaa anti-3.7 triplication are only sporadically known [23]. The aaa anti-3.7 triplication was found lower than -a 3.7 deletion in our study, similar to other studies worldwide.…”

Identification of patients with defects in the globin genes by analysing blood parameters and genetic study: Report of five cases

“…The molecular analysis of the alfa globin genes highlighted an anti 3.7 Kb gene triplication heterozygous mutation (see Figure 2). Carriers of this mutation show no clinical symptoms or hematological changes, although a considerable amount of literature has reported that the existence of this mutation with mutations in β globin genes worsens the clinical characteristics of the patient, as it has been found in this case [9] . Figure 1.…”

Alpha thalassemia gene mutations in neonates from Mazandaran, Iran, 2012

“…4 Nevertheless, in another study on Tehran population, the frequency of this mutation was reported to be close to Mazandaran (2.14%). 20 Comparing all the available studies in different provinces of Iran, one may conclude that the total carrier frequency of alpha globin gene mutations is similar in different regions of Iran; however, the spectra of mutations Comparing to Mazandaran province, frequency of alpha thalassemia carriers is higher in UAE, but it has to be noted this high frequency rate is mostly due to high allelic frequency of -α 3.7 deletion in that population (0.2847 in UAE versus 0.0485 in Mazandaran), but if we compare the next common mutations in the two populations, we realize that other mutations do not have very high frequencies in UAE and for instance, -α 4.2 deletion which is the second most common mutation in both societies, has a higher allelic frequency rate in Mazandaran (0.0072 versus 0.0206). The results of similar studies from Southeast Asia, Brazil, and Georgia have shown that carriers with -α 3.7 deletion are more common than other alpha thalassemia gene mutations, and this mutation has to be considered the most common alpha globin gene mutation worldwide.…”