Rare alpha(0)-thalassemia deletions detected by MLPA in five unrelated Brazilian patients

Author(s)

Mota, Natalia O. ^[1] ; Kimura, Elza M. ^[1] ; Ferreira, Roberta D. ^[1] ; Pedroso, Gisele A. ^[1] ; Albuquerque, Dulcineia M. ^[2] ; Ribeiro, Daniela M. ^[1] ; Santos, Magnun N. N. ^[1] ; Bittar, Cristina M. ^[3] ; Costa, Fernando F. ^[2] ; Sonati, Maria de Fatima ^[1]

Affiliation

^[1] Univ Estadual Campinas UNICAMP, Fac Ciencias Med, Dept Patol Clin, Lab Hemoglobinopatias, Campinas, SP - Brazil

^[2] Univ Estadual Campinas UNICAMP, Hemoctr, Campinas, SP - Brazil

^[3] Hosp Clin Porto Alegre, Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: GENETICS AND MOLECULAR BIOLOGY; v. 40, n. 4, p. 768-773, OCT-DEC 2017.
• Web of Science Citations: 2

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 alpha-globin genes, located on chromosome 16p13.3, are the main causes of alpha-thalassemia. Multiplex ligation-dependent probe amplification (MLPA) can be used to detect rearrangements that cause alpha-thalassemia, particularly large deletions involving the whole alpha cluster and/or deletions in the HS-40 region. Here, MLPA was used to investigate the molecular basis of alpha-thalassemia in five unrelated patients, three of whom had Hb H disease. In addition to the -alpha(3.7) deletion identified in the patients with Hb H disease, four different alpha(0) deletions removing 15 to 225 kb DNA segments were found: two of them remove both the alpha genes, one affects only the regulatory element (HS-40) region, and another one extends over the entire alpha cluster and the HS-40 region. These results illustrate the diversity of alpha-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 A(2) levels. (AU)

• FAPESP's process: 14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches
• Grantee: Fernando Ferreira Costa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/21184-8 - THP-1 culturing cells standardization to evaluate miRNAs and their target genes response against influence of anti-inflammatory stimuli
• Grantee: Roberta Dorta Ferreira
• Support Opportunities: Scholarships in Brazil - Scientific Initiation