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Alpha thalassemia and alpha-MRE haplotypes in Uruguayan patients with microcytosis and hypochromia without anemia.

ABSTRACT: Alpha thalassemia is the most common genetic disorder across the world, being the α-3.7 deletion the most frequent mutation. In order to analyze the spectrum and origin of alpha thalassemia mutations in Uruguay, we obtained a sample of 168 unrelated outpatients with normal hemoglobin levels with microcytosis and hypochromia from two cities: Montevideo and Salto. The presence of α-thalassemia mutations was investigated by gap-PCR, restriction endonucleases analysis and HBA2 and HBA1 genes sequencing, whereas the alpha-MRE haplotypes were investigated by sequencing. We found 55 individuals (32.7%) with α-thalassemia mutations, 51(30.4%) carrying the -α3.7 deletion, one with the -α4.2 deletion and three having the rare punctual mutation HBA2:c.-59C>T. Regarding alpha-MRE analysis, we observed a significant higher frequency of haplotype D, characteristic of African populations, in the sample with the -α3.7 deletion. These results show that α-thalassemia mutations are an important determinant of microcytosis and hypochromia in Uruguayan patients with microcytosis and hypochromia without anemia, mainly due to the -α3.7 deletion. The alpha-MRE haplotypes and the α-thalassemia mutations spectrum suggest a predominant, but not exclusive, African origin of these mutations in Uruguay.

SUBMITTER: Soler AM

PROVIDER: S-EPMC7995682 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLow HbA2 level is an underlying of δ-thalassemia, α-thalassemia, and IDA. Interactions of these disorders can generate a wide spectrum of phenotype, which will pose diagnostic conundrum for clinical assessment, carrier screening, and genetic counseling.MethodsSubjects with HbA2 levels below 2.0% with normal or reduced hematological parameters were recruited for further investigation. δ-globin gene mutations were identified by DNA sequencing of the HBD gene. Serum ferritin (SF) concentration was determined by the chemiluminescent microparticle immunoassay. The three common deletional α-thalassemia (--SEA /αα, -α3.7 /αα, and -α4.2 /αα) were detected using Gap-PCR, detection of the point mutations in the three nondeletional α-thalassemia (αCS α/αα,αQS α/αα,αWS α/αα), and the 17 common β-thalassemia was performed using reverse dot blot hybridization (RDB).ResultsWe had characterized the δ-globin gene mutations in 20 cases, revealing a frequency of 0.4% in the women of reproductive age (20/4 792). Two previously known mutations:-77 T > C and -30 T > C and 3 novel δ-globin gene defects: -44G > A,CD87C > T, and CD134T > A were found. In the selected cases, we also found 85 cases confirmed with (51.2%,85/166) IDA and 39 cases (23.5%,39/166) with common α-thalassemia. Subjects with δ-thalassemia had statistically higher levels of Hb, MCV, and MCH compared with other two groups, whereas statistically lower levels of RDW were seen in δ-thalassemia group. What's more, statistically higher levels of SF were seen in δ-thalassemia group, compared with IDA groups.ConclusionWe reported the spectrum of δ-thalassemia mutations for the first time with the frequency of 0.4% among women of reproductive age in Fujian area and found that -77T > C mutation was the most common mutation, followed by -30T > C mutation. What's more, 3 novel δ-globin gene defects: -44G > A,CD87C > T and CD134T > A were found. A thorough analysis of the hematological, electrophoretic characterization, and the level of SF was needed to suspect and further investigate the existence of IDA, α-thalassemia, and δ-thalassemia.

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Alpha thalassemia and alpha-MRE haplotypes in Uruguayan patients with microcytosis and hypochromia without anemia.

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