Distribution of HBB Gene Mutations in the Kurdish Population of Ilam Province, West Iran

Alibakhshi

Kazeminia

2021

Self Cite

Background The quantification of hemoglobin A2 (Hb A2; α2δ2) is used as a valuable test to differentiate α- and ß-thal carriers in clinical laboratories. Therefore, the HBD (δ-globin) gene variants could result in reduced levels of Hb A2 and have implications for thalassemia screening programs. The aim of the present study was to predict the consequences of HBD gene variants identified in the Iranome project. Results The highest number of variants was in the Persian Gulf Islanders. The variants of p.Gln132Glu (HBD: c.394C>G), p.Gly17Arg (HBD: c.49G>C), p.Thr5Ile (HBD: c.14C>T), and p.Ala28Ser (HBD: c.82G>T) presented damage results in three or more prediction tools. In addition, it seems that the p.Gly30= (HBD: c.90C>T) decreases the use of authentic splice and, instead, creates a new donor splice site (DSS) or leads to the use of a cryptic DSS. Conclusions Most of these variants have been associated with a decrease in Hb A2 levels. Due to the high mutational diversity in the HBB gene in the Iranian population and the use of Hb A2 quantification to differentiate α- and ß-thal carriers among Iranian clinical laboratories, some attention should be taken to a possible co-inheritance of HBD gene variants to avoid the misdiagnosis of ß-thal carriers.

Section: Discussionmentioning

confidence: 99%

In silico prediction of HBD gene variants in the Iranian population

Alibakhshi

Kazeminia

2021

Self Cite

Problem of borderline hemoglobin A2 levels in an Iranian population with a high prevalence of α- and β-thalassemia carriers

Alibakhshi

Shafieenia

et al. 2022

Background It is difficult to classify a small fraction of α- and β-thalassemia (α- and β-thal) carriers based on their Hb A2 levels. Here, we report the results of a molecular investigation in a cohort of thalassemia carriers with borderline Hb A2 levels originated from western Iran. Results The documents of 5956 α- or β-thal carriers were reviewed. The frequency of individuals with borderline Hb A2 levels in this cohort was 436 (7.32%). A total of 12 different α-thal and 27 different β-thal variants were identified in this study. Conclusions Our data showed that individuals with borderline Hb A2 are not uncommon in our population. Moreover, preselection of α- and β-thal carriers with borderline Hb A2 levels based on Hb A2, mean corpuscular volume (MCV), and mean cell hemoglobin (MCH) is not advisable in our population. Therefore, it is necessary to investigate both α- and β-globin genes in cases with borderline Hb A2 levels, especially if the partner is a carrier of β-thal or α0-thal.

In silico analysis and the pathogenicity classification of PTS gene variants among Iranian population

Khamooshian

Kazeminia

2022

Background 6-Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is an autosomal recessive disorder caused by PTS gene mutations. The aim of this study was to collect all PTS gene variants detected among Iranian patients with PTPS deficiency as well as in the Iranome project and classify them based on American College of Medical Genetics and Genomics (ACMG-AMP) guidelines. Results The number of PTS gene variants reported among Iranian PTPS patients and in the Iranome project were 19 and 36, respectively. Given that one variant was reported in both of our sources, the total number of variants was 54. These variants were classified as pathogenic (n = 11), likely pathogenic (n = 7), VUS (n = 23), likely benign (n = 1), and benign (n = 12). Out of 19 variants reported among Iranian PTPS patients, c.155A>G (p.Asn52Ser, rs104894275) and c.317C>T (p.Thr106Met, rs200712908) were the most frequent ones, each with a frequency of 10%. c.84-3C>G (rs1230781262) (7.5%) and c.281A>T (p.Asp94Val) (5%) were in the next ranks of the list of variants. Conclusions The ACMG-AMP criteria need to be updated depending on the type of disease. In addition, to the best of our knowledge, no template has been described for classifying the variants identified in PTPS deficiency. Therefore, this study can be a good reference for future studies in this subject.