RESUMO
Hb J Sardegna is a well known innocent Hb variant which is widespread in Sardinia. As yet, homozygosity for Hb J Sardegna has not been documented. This report deals with the homozygous state for Hb J which we demonstrate by molecular analysis in two Sardinian siblings in which beta-thalassemia coexists. The Hb J specific mutation was determined both by enzyme digestion and by sequencing specific segments of PCR amplified alpha-globin genes. A pregnant girl showed mild non-sideropenic microcytic anemia, normal Hb A(2) levels (2.4%) on DE-52 microchromatography, 50% of Hb variant on HPLC and 2.1 alpha/beta globin chain biosynthetic ratio. She proved to be a carrier of the beta degrees 6(-A) thalassemia determinant. The alpha-globin gene mapping did not reveal alpha-thalassemia. Btg I restriction analysis of both alpha(2)-globin genes showed a recognition site defect for this enzyme in both chromosomes, which resulted to be the C-->A point mutation in homozygosity at the first nt of alpha(2)-globin gene 50th codon by sequencing. This defect, typical of Hb J Sardegna, was also present in her brother. From a practical point of view, this study demonstrates that the association of beta-thalassemia with Hb J, may show falsely reduced Hb A(2) levels on routine Hb A(2) quantitation techniques, such as DE-52 microchromatography. This possibility implies that identification methods such as simple Hb electrophoresis, which permit visualization of Hb A(J)(2) should be used in thalassemia screening involving populations in which Hb J and beta-thalassemia coexist.