Rare α0-thalassemia deletions detected by MLPA in five unrelated Brazilian patients

Abstract

Alpha-thalassemias are among the most common genetic diseases in the world. They are characterized by hypochromic and microcytic anemia and great clinical variability, ranging from a practically asymptomatic phenotype to severe anemia, which can lead to intrauterine or early neonatal death. Deletions affecting the α-globin genes, located on chromosome 16p13.3, are the main causes of α-thalassemia. Multiplex ligation-dependent probe amplification (MLPA) can be used to detect rearrangements that cause α-thalassemia, particularly large deletions involving the whole α cluster and/or deletions in the HS-40 region. Here, MLPA was used to investigate the molecular basis of α-thalassemia in five unrelated patients, three of whom had Hb H disease. In addition to the -α3.7 deletion identified in the patients with Hb H disease, four different α0 deletions removing 15 to 225 kb DNA segments were found: two of them remove both the α genes, one affects only the regulatory element (HS-40) region, and another one extends over the entire α cluster and the HS-40 region. These results illustrate the diversity of α-thalassemia deletions in the Brazilian population and highlight the importance of molecular investigation in cases that present with microcytosis and hypochromia without iron deficiency and normal or reduced Hb A2 levels..

Alpha-Thalassemia in North Morocco: Prevalence and Molecular Spectrum

“…HS-40 deletion allele and α 0 - -Med-I allele were found in lower frequencies (0.03% each). HS-40 deletion, already reported in the Brazilian population [43] but never in North Africa and Middle East [38, 44], is caused by the loss of the major regulatory element of the human alpha-globin locus, located 40 kb upstream of the zeta-globin gene, essential for α globin expression. - - MED-I, also responsible for α 0-thalassaemia, is relatively frequent in Greece, Turkey, and the Middle East [3].…”

Breakpoint characterization of a rare alpha0‐thalassemia deletion using targeted locus amplification on genomic DNA

“…While Phylipsen et al, 16 had characterized the ‐‐ gb deletion to be 16 771 bp in three Dutch individuals, the corresponding Ithanet page: IthaID: 3292, describes a 15 kb deletion. Additionally, Mota et al, 17 found this deletion in a Brazilian patient solely by MLPA and registered this deletion as the 15.2 kb ‐‐ gb on Ithanet (IthaID: 3296) without determining the breakpoint. Consequently, it is not certain that the deletion found in the Brazilian patient is identical to the ‐‐ gb deletion.…”

Analysis of rare thalassemia caused by HS-40 regulatory site deletion

“…In this case, in addition to the -α3.7 deletion on one allele of the chromosome (heterozygous), only one α-globin gene was expressed on one allele, and HS-40 deletion was present on the other allele of the chromosome (heterozygous), which affected the expression of the two downstream α-globin genes, eventually manifesting as Hb H disease; this is consistent with related reports. In addition to the -3.7 deletion, four different deletions removing 15-225 kb DNA segments were found in a study: two of them eliminated both the genes, one affected only the regulatory element (HS-40) region, and another one extended over the entire cluster and the HS-40 region, manifesting as Hb H disease [13]. It is important to point out that in a previous study, a homozygous HS-40 deletion was found in an 11-year-old boy, who only manifested as Hb H disease.…”