In order to determine the contribution of a-thalassemia to microcytosis and hypochromia, 339 adult outpatients seen at Unicamp University Hospital (with the exception of the Clinical Hematology outpatient clinics), who showed normal hemoglobin (Hb) levels and reduced mean corpuscular volume and mean corpuscular hemoglobin, were analyzed. Ninety-eight were Blacks (28.9%) and 241 were Caucasians (71.1%). In all cases, Hb A 2 and F levels were either normal or low. The most common deletional and nondeletional forms of a-thalassemia [-a 3.7 , -a 4.2 , --MED , -(a) 20.5 , a HphI a, a NcoI a, aa NcoI and a TSAUDI ] were investigated by PCR and restriction enzyme analyses. A total of 169 individuals (49.9%) presented a-thalassemia: 145 (42.8%) were heterozygous for the -a 3.7 deletion (-a 3.7 /aa) and 18 (5.3%) homozygous (-a 3.7 /-a 3.7 ), 5 (1.5%) were heterozygous for the nondeletional form a HphI a (a HphI a/aa), and 1 (0.3%) was a --MED carrier (--MED /aa). Among the Blacks, 56 (57.1%) showed the -a 3.7 / aa genotype, whereas 12 (12.2%) were -a 3.7 /-a 3.7 and 1 (1.0%) was an a HphI a carrier; among the Caucasians, 89 (36.9%) were -a 3.7 /aa, 6 (2.5%) had the -a 3.7 /-a 3.7 genotype, 4 (1.7%) presented the nondeletional form (a HphI a/aa), and 1 (0.4%) was a --MED carrier. These results demonstrate that a-thalassemia, mainly through the -a 3.7 deletion, is an important cause of microcytosis and hypochromia in individuals without anemia. These data are of clinical relevance since these hematological alterations are often interpreted as indicators of iron deficiency.

Seven unrelated patients with hemoglobin (Hb) H disease and 27 individuals with a -chain structural alterations were studied to identify the a -globin gene mutations present in the population of Southeast Brazil. The -a 3.7 , --MED and -(a) 20.5 deletions were investigated by PCR, whereas non-deletional a -thalassemia (a Hph a , a NcoI

We are reporting here the results of differential gene expression experiments comparing two siblings, a 21-yr-old male and a 19-yr-old female, with the same alpha-thalassemia genotype (-alpha(3.7)/(--SEA)) and quite different levels of Hb H in the peripheral blood (18.7 and 5%, respectively). By using mRNA differential-display reverse-transcription-PCR and suppression subtractive hybridization, two main transcripts were selected in both procedures and validated by qRT-PCR, one corresponding to the phosphatidylinositol phosphate 4-kinase type II-alpha (PIP4KIIA) gene and the other to the beta-globin gene, both over expressed in the patient with the higher percentage of Hb H. Type II PIP kinases produce phosphatidylinositol 4,5 biphosphate, a critical and pleiotropic regulatory molecule involved in diverse cellular activities, including gene expression. Our results suggest that PIP4KIIA may be one of the factors related to the regulation of the beta-globin gene expression and the different levels of Hb H in alpha-thalassemic patients.

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.

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