Alpha‐globin gene triplication and its effect in beta‐thalassemia carrier, sickle cell trait, and healthy individual

Abstract

The genotype and phenotype correlation between coinheritance of heterozygous beta‐thalassemia with the alpha‐globin triplication is unclear. In this study we have investigated and reviewed alpha triplication frequency in beta‐thalassemia carriers, sickle cell trait, and healthy individuals and its effect on hematological and phenotypical changes. In this study, 4005 beta‐thalassemia carriers, 455 sickle cell trait, and 2000 healthy individuals were included. Molecular characterization of beta and alpha‐thalassemia was performed. The frequencies of alpha‐globin triplication in beta‐thalassemia carriers, sickle cell trait, and healthy individuals were 67 (1.67%), 4 (0.88%), and 18 (0.9%), respectively. In total, the frequency of alpha‐triplications is approximately 89 (1.39%) in Khuzestan province, South of Iran population. We have compared the average hematological parameters of beta‐thalassemia carriers, sickle cell trait, and healthy individuals with and without alpha gene triplication. This mutation did not show any significant effect on the change of blood indices, neither in healthy individuals nor in sickle cell trait and beta‐thalassemia carriers. Therefore, there is no need to take more notice of anti 3.7 mutation in beta‐thalassemia carriers is opposed with some studies reported that the presence of excess alpha‐globin genes in beta‐thalassemia carriers can lead to the phenotype of beta‐thalassemia intermedia. Therefore, not every individual with triplicated alpha globin coinherited with beta‐thalassemia trait will have a significantly lower Hb than normal, and it is highly likely that none of them will need transfusion.

Hematological and genetic profiles of persons with co‐inherited heterozygous β‐thalassemia and supernumerary α‐globin genes

“…Four out of the 16 cases by Camashella et al, 15 had received blood transfusions. None of the 67 cases of Hamid et al, 11 or the six cases previously described from our center by Trehan et al had ever required a transfusion. Abedini et al, 14 reported that 10 (27.8%) of their cases had been intermittently transfused while 15 (41.7%) were regularly transfused.…”

“…The wide-ranging clinical phenotypes were also reported by Mehta et al, 18 with 25 index cases having a βTI-like syndrome, and 10 family members of index cases being asymptomatic. In contrast, Hamid et al, 11 from Iran reported that their all 67 subjects had βTT-like (mild/asymptomatic) phenotypes. However, another…”

“…The wide‐ranging clinical phenotypes were also reported by Mehta et al, 18 with 25 index cases having a βTI‐like syndrome, and 10 family members of index cases being asymptomatic. In contrast, Hamid et al, 11 from Iran reported that their all 67 subjects had βTT‐like (mild/asymptomatic) phenotypes. However, another Iranian study by Abedini et al, evaluated 36 subjects with a wide range of hemoglobins (6.8–12.0 g/dl) and 6 being post‐splenectomy, suggesting greater phenotypic variations 14 .…”

“…Globally, the largest study by Hamid et al 11 from the Pasteur Institute in Tehran, Iran analyzed 67 βTT with supernumerary α-globin genes.…”

“…We report the largest Indian patient cohort (and the second largest in the world) with co‐inherited βTT + supernumerary α‐globin genes. Globally, the largest study by Hamid et al 11 from the Pasteur Institute in Tehran, Iran analyzed 67 βTT with supernumerary α‐globin genes. Case numbers in other studies and case series from different countries range from 31 to 5 12–17 .…”