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Fetal hemoglobin elevation in Hb lepore heterozygotes and its correlation with β globin cluster linked determinants
Author(s) -
Gonçalves Isabel,
Henriques Ana,
Raimundo Ana,
Picanço Isabel,
Reis Ana,
Correia Jr. Esmeraldina,
Santos Ester,
Nogueira Paulo,
OsórioAlmeida Leonor
Publication year - 2002
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.10019
Subject(s) - genetics , haplotype , fetal hemoglobin , compound heterozygosity , heterozygote advantage , biology , allele , mutation , thalassemia , hemoglobinopathy , gene , hemolytic anemia , fetus , immunology , pregnancy
Abstract We have analysed, at the hematological and molecular level, 51 Hb lepore heterozygotes and three compound heterozygotes for Hb Lepore and HbS (HbLep/HbS) in 26 unselected Portuguese families. The Lepore Boston variant was present in one family, in association with classical haplotype V. All of the other Lepore alleles present haplotype III in association with Xmn I (+)5′ of G γ gene, in tight linkage disequilibrium to the major mutation found in the Portuguese population, the Lepore Baltimore variant ( δ 68Leu ‐β 84Thr ). The three compound heterozygotes are the first HbLep/HbS individuals reported in the literature, with the Lepore Baltimore mutation linked to haplotype III. In agreement with other studies, these Lepore Baltimore heterozygotes have higher HbF (1.4–14.1% of total hemoglobin) than published cases of Lepore Boston (0.8–5.4%), which is associated with Xmn I(–). Among the Lepore Baltimore heterozygotes, the (AT) x T y repeat region at –540 bp of the β globin gene in trans to the Lepore chromosome, can account for much of the variability in HbF level. The allele (AT) 7 T 7 is associated with lower HbF, and (AT) 9 T 5 is associated with higher HbF. As we previously reported for β thalassemic carriers, we observe in Lepore Baltimore carriers an effector in trans , linked to the (AT) x T y sequence, acting as an HPFH (Hereditary Persistence of Fetal Hemoglobin) determinant. Am. J. Hematol. 69:95–102, 2002. © 2002 Wiley‐Liss, Inc.