alpha-globin genes: thalassemic and structural alterations in a Brazilian population

Seven unrelated patients with hemoglobin (Hb) H disease and 27 individuals with alpha-chain structural alterations were studied to identify the alpha- globin gene mutations present in the population of Southeast Brazil. The -a lpha(3.7),-(MED) and -(alpha)(20.5) deletions were investigated by PCR, whe reas non-deletional alpha-thalassemia (alpha(Hph)alpha, alpha(NcoI)alpha, a lpha alpha(NcoI), alpha(Ic)alpha and alpha(TSaudi)alpha) was screened with restriction enzymes and by nested PCR, Structural alterations were identifi ed by direct DNA sequencing. Of the seven patients with Hb H disease, all o f Italian descent, two had the -(alpha)(20.5)/-alpha(3.7) genotype, one had the -(MED)/-alpha(3.7) genotype, one had the -(MED)/alpha(Hph)alpha genoty pe and three showed interaction of the -alpha(3.7) deletion with an unusual , unidentified form of non-deletional alpha-thalassemia [-alpha(3.7)/(alpha alpha)(T)]. Among the 27 patients with structural alterations, 15 (of Ital ian descent) had Hb Hasharon (alpha 47Asp-->His) associated with the -alpha (3.7) deletion, 4 (of Italian descent) were heterozygous for Hb J-Rovigo (a lpha 53Ala-->Asp), 4 (3 Blacks and 1 Caucasian) were heterozygous for Hb St anleyville-II (alpha 78Asn-->Lys) associated with the alpha(+)-thalassemia, 1 (Black) was heterozygous for Hb G-Pest (alpha 74Asp-->Asn), 1 (Caucasian ) was heterozygous for Hb Kurosaki (alpha 7Lys-->Glu), 1 (Caucasian) was he terozygous for Hb Westmead (alpha 122His-->Gln), and 1 (Caucasian) was the carrier of a novel silent variant (Hb Campinas, alpha 26Ala-->Val). Most of the mutations found reflected the Mediterranean and African origins of the population. ribs G-Pest and Kurosaki, very rare, and Hb Westmead, common i n southern China, were initially described in individuals of ethnic origin differing from those of the carriers reported in the present study and are the first cases to be reported in the Brazilian population.