HEMOGLOBIN, vol.21, no.1, pp.41-51, 1997 (SCI-Expanded)
A total of 25 unrelated Hb H patients were studied at the DNA level. Ten different genotypes were found to be responsible for the disease. The most prevalent alpha-thalassemia-2 determinant was the alpha alpha/-alpha(3.7) kb deletion (56%) which was followed by a nondeletional type of alpha-thalassemia, namely the pentanucleotide deletion in the 5' first intervening sequence splice junction [alpha(-5nt)alpha] (16%). The two most frequent alpha-thalassemia-1 determinants were alpha alpha/-20.5 kb and alpha alpha/-17.5 kb (MED-I) deletions. In two patients, homozygosity for the polyadenylation signal mutation [alpha(PA-2)alpha] was found to be responsible for Hb H disease. Clinical and hematological expression seems more severe in patients with the alpha(-5nt)alpha deletion at the donor site of the first intervening sequence and the alpha(PA-2)alpha mutation in trans to an alpha-thalassemia-1 determinant. Homozygosity for the alpha(PA-2)alpha mutation was also found to be associated with severe phenotype.