Characterization of alpha thalassemic genotypes by multiplex ligation-dependent probe amplification in the Brazilian population

Author(s)

Suemasu, C. N. ; Kimura, E. M. ; Oliveira, D. M. ; Bezerra, M. A. C. ^[1] ; Araujo, A. S. ^[2] ; Costa, F. F. ^[3] ; Sonati, M. F. ^[4]

Affiliation

^[1] Univ Fed Pernambuco, Ctr Ciencias Biol, Recife, PE - Brazil

^[2] Fundacao Hematol & Hemoterapia Pernambuco, Recife, PE - Brazil

^[3] Univ Estadual Campinas, Ctr Hematol & Hemoterapia, BR-13083970 Campinas, SP - Brazil

^[4] Univ Estadual Campinas, Dept Patol Clin, Fac Ciencias Med, UNICAMP, Lab Hemoglobinopatias, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: Brazilian Journal of Medical and Biological Research; v. 44, n. 1, p. 16-22, JAN 2011.
• Web of Science Citations: 6

Abstract

Alpha-thalassemia is the most common inherited disorder of hemoglobin synthesis. Genomic deletions involving the alpha-globin gene cluster on chromosome 16p13.3 are the most frequent molecular causes of the disease. Although common deletions can be detected by a single multiplex gap-PCR, the rare and novel deletions depend on more laborious techniques for their identification. The multiplex ligation-dependent probe amplification (MLPA) technique has recently been used for this purpose and was successfully used in the present study to detect the molecular alterations responsible for the alpha-thalassemic phenotypes in 8 unrelated individuals (3 males and 5 females; age, 4 months to 30 years) in whom the molecular basis of the disease could not be determined by conventional methods. A total of 44 probe pairs were used for MLPA, covering approximately 800 kb from the telomere to the MSLN gene in the 16p13.3 region. Eight deletions were detected. Four of these varied in size from 240 to 720 kb and affected a large region including the entire alpha-globin gene cluster and its upstream regulatory element (alpha-MRE), while the other four varied in size from 0.4 to 100 kb and were limited to a region containing this element. This study is the first in Brazil to use the MLPA method to determine the molecular basis of alpha-thalassemia. The variety of rearrangements identified highlights the need to investigate all cases presenting microcytosis and hypochromia, but without iron deficiency or elevated hemoglobin A(2) levels and suggests that these rearrangements may be more frequent in our population than previously estimated. (AU)

• FAPESP's process: 10/00560-8 - Caracterization of deletional alpha-thalasssemic genotypes by MLPA
• Grantee: Maria de Fatima Sonati
• Support type: Regular Research Grants
• FAPESP's process: 08/57441-0 - Clinical, cellular and molecular alterations in hemoglobinopathies and other hereditary hemolytic anemias
• Grantee: Fernando Ferreira Costa
• Support type: Research Projects - Thematic Grants