Hemoglobin H disease resulting from the association of the – α^3.7 rightward deletion and the (αα)^ΜΜ deletion in a Brazilian patient

Abstract

A patient with Hb H disease resulting from the association of the - alpha 3.7 rightward deletion with the rare (alpha alpha)MM deletion, which removes the entire alpha-major regulatory element (MRE), is reported. This is the first description of an alpha-thalassemic mutation resulting from deletion of the locus-controlling sequences in the South-American population.

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

“…Although the exact breakpoint positions and deletion lengths could not be determined at the time of the study, the deletions found in 6 patients (P1, P2, P3, P6, P7, and P8) are close in terms of size and genome position to previously described alterations (10,24,26,27,31). Two deletions, found in patients 4 and 5, showed no resemblance to previously described deletions and are possibly novel.…”

“…These deletions span a region of at least 0.4 kb in 1 case and from 95 to 100 kb in the others [positions 163464-163904, 97000-193847, 97000-202417, and 97000-202417 of the UCSC Genome Browser (21), February 2009, respectively]. Since the first description of a deletion of this type, which removes 62 kb including the HS-40 element (22), deletions involving this region have been described in more than 20 patients (10,15,(23)(24)(25)(26)(27)(28)(29)(30)(31). The regulatory element α-MRE behaves as a classic enhancer: its main function in the normal chromosomal environment is to activate and enhance expression from the ζ-globin and α-globin promoters (32).…”

“…Although α-thalassemia is present throughout the world, its distribution varies greatly among different populations. In Brazil, most of the recognized α-thalassemia mutations involve deletions of one α-globin gene (α + -thalassemias), although several cases of α 0 -thalassemias have been reported in the literature (8)(9)(10)(11)(12). It has been shown that the -α 3.7 deletion is the most frequent mutation in the Brazilian population, occurring in 20-25% of the black population in the Southeastern region of the country (13).…”

Molecular and Hematological Characterization of Hemoglobin H Disease in the Bengali Population of Kolkata, India

“…Many cases of HbH disease were documented worldwide (Chen et al, 2000;Kanavakis et al, 2000;Wenning et al, 2000;Liu et al, 2000;Waye et al, 2001;Higgs, 2001;Zorai et al, 2002Zorai et al, , 2003Eng et al, 2005;Li et al, 2005;Origa et al, 2006;Chan et al, 2007;Sura et al, 2007). Some cases of HbH diseases have been found in the newborn in West Bengal, and in Bombay, 2% and 4% of cord samples contained Hb Bart's (Chouhan et al, 1970;Mitra, 1983).…”

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

“…In Brazil, its prevalence is high ( Sonati et al , 1991 ; Couto et al , 2003 ; Adorno et al , 2005 ; Wagner et al , 2010 ; Cardoso et al , 2012 ; De Medeiros Alcoforado et al , 2012 ). However, Hb H disease, which is found primarily in Southeast Asia, the Middle East and the Mediterranean, has only rarely been reported in Brazil, where most cases are the result of an interaction of the -α 3.7 deletion with the -- MED , -(α) 20.5 , or -- SEA deletions ( Sonati et al , 1992 ; Wenning et al , 2000 , 2002 , 2009 ; Kimura et al , 2009 ). Combinations of the -α 3.7 deletion with new or rare α 0 deletions started to be detected in the Brazilian population more recently, suggesting that the prevalence of Hb H disease may be underestimated ( Suemasu et al , 2011 ).…”