Identification of β thalassemia mutations in South Brazilians

Abstract

We have evaluated the mutation profile in a sample of 127 unrelated beta-thalassemia (beta thal) individuals, diagnosed through A2 and fetal hemoglobin quantification by high-performance liquid chromatography (HPLC) from the Brazilian southernmost state, where a flow of Italian immigrants had occurred in the late 19th century, mainly from Northern Italy. The molecular analysis was performed by DNA sequencing of the most common mutations found in the Mediterranean region. The beta 0 codon 39 nonsense mutation was the most frequent alteration (50.9%), followed by beta+ IVSI 110 G>A (18.1%), beta 0 IVSI 1 G>A (12.9%), beta+ IVSI 6 T>C (9.5%), and other rare mutations (8.6%). The chosen gene sequence was able to identify 91% beta-thal mutations in the population studied, showing some similarity with allele frequencies of the mainly colonizing countries of Rio Grande do Sul state. The comparison of our results to other Brazilian studies has shown significant differences. Therefore, we can conclude that the genotypic profile of beta-thal shows great variability. Hence, it would be arbitrary to infer regional study results as being representative of the Brazilian whole population. Brazilian researchers of different regions should identify their most frequent genotypes to provide better understanding on this disease and state adequate public health policies.

High Resolution Melting Analysis: A Rapid Screening and Typing Tool for Common β-Thalassemia Mutation in Chinese Population

“…Traditional method of β-thalassemia screening including hematological parameters and hemoglobin electrophoresis could not be applied for dry blood spots of neonates. Some techniques could be used for screening β-thalassemia by dry blood spots, such as high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) [20], [21], and amplification refractory mutation system-PCR, PCR-SSCP, denaturing high performance liquid chromatography (DHPLC), matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF) and PCR-RDB [6]. However, these methods are time consuming and costly for large scale screening.…”

Anti-Toxoplasma gondii antibodies in patients with beta-hemoglobinopathies: the first report in the Americas

“…Because high frequencies of some mutations of beta-thalassemia are found in the Brazilian population [23, 24], the following were investigated: CD39 (HBB: c.118C>T), IVSI-110 (HBB: c.93-21G>A), IVSI-6 (HBB: c.92 + 6T>C) and IVSI-1 (HBB: c.92 + 1G>A). Detection of these mutations was performed by allele-specific PCR, using the PS39 W (5′ GAC TCA AAG AAC CTC TG 3′) and PS39M primers (5′ GAC TCA AAG AAC CTC TA 3′) for the CD39 mutation; the TB110W (5′ GGG TGG GAA AAT AGA CC 3′) and TB110M primers (5′ GGG TGG GAA AAT AGA CT 3′) for the IVSI-110 mutation; the IVSI6W (5′ GTC TTG TAA CCT TGA TA 3′) and IVSI6M primers (5′ GTC TTG TAA CCT TGA TG 3′) for the IVSI-6 mutation and the IVSI1W (5′ GTG ACC TTG ATA CCA AC 3′) and IVSI1M primers (5′ GTG ACC TTG ATA CCA AA 3′) for IVSI-1 mutation.…”

Prevalence of common α-thalassemia determinants in south Brazil: importance for the diagnosis of microcytic anemia

“…Multivariate Analysis of Variance (MANOVA) was used to compare these adjusted variables, as well as the mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC), with the corresponding values in patients with microcytic anemia (several α-genotypes), in a previously characterized group of 124 β-thalassemia trait carriers from the same population (Reichert et al , 2008) and in healthy (control) volunteers. The SNK procedure was used for subsequent pairwise multiple comparisons between groups, except for RBCs, for which Tamhanes test was used to account for heterocedasticity.…”

“…In contrast to ß -thalassemia carriers, for which important regional differences in the mutational profile have been identified in Brazilian populations (Reichert et al , 2008), α-thalassemias show considerably less variability, which greatly facilitates the implantation of adequate public health policies and diagnostic services for dealing with this frequent genetic trait and for diagnosing microcytosis. In this context, the data reported here may serve as potential reference values for the detection of Brazilian patients suspected of having thalassemia.…”