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..
In Uruguay, α-thalassemia (α-thal) mutations were introduced predominantly by Mediterranean European immigrant populations and by slave trade of African populations. A patient with anemia with hypochromia and microcytosis, refractory to iron treatment and with normal hemoglobin (Hb) electrophoresis was analyzed for α-thal mutations by multiplex gap-polymerase chain reaction (gap-PCR), automated sequencing and multiplex ligation-dependent probe amplification (MLPA) analyses. Agarose gel electrophoresis of the multiplex gap-PCR showed a band of unexpected size (approximately 700 bp) in the samples from the proband and mother. Automated sequencing of the amplified fragment showed the presence of the -(α)(5.2) deletion (NG_000006.1: g.32867_38062del5196) [an α-thal-1 deletion of 5196 nucleotides (nts)]. The MLPA analysis of the proband's sample also showed the presence of the -(α)(5.2) deletion in heterozygous state. We report here the presence of the -(α)(5.2) deletion, for the first time in the Americas, in a Uruguayan family with Italian ancestry, detected with a previously described multiplex gap-PCR.
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