Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program

Abstract

ObjectiveTo characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. MethodsβS allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI) were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. ResultsThe following alpha chain variants were found: seven children with hemoglobin Hasharon [alpha2 47(CE5) Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13) Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2) Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5) Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. ConclusionApparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

Investigating alpha-globin structural variants: a retrospective review of 135,000 Brazilian individuals

“… 40,41 In this respect, different alpha-globin variants have been found in other Brazilian regions, such as in the state of Minas Gerais, where Hb Etobicoke, Hb Ottawa and Hb St. Luke's were detected for the first time in Brazil. 42 …”

α-chain hemoglobin variants with electrophoretic mobility similar to that of hemoglobin S in newborn screening programs

“…The most commonly used screening methods in Brazil are isoelectric focusing and HPLC, followed by molecular biology techniques (16) . In the National Neonatal Screening Program operated by the Brazilian national health system (SUS), the heel prick, which is carried out in most Brazilian maternity wards, is used to screen for SCD and other genetic diseases (1) .…”

“…In the National Neonatal Screening Program operated by the Brazilian national health system (SUS), the heel prick, which is carried out in most Brazilian maternity wards, is used to screen for SCD and other genetic diseases (1) . With the aid of this screening program various α-chain variants have been detected, as the article published in this issue by Silva et al (17) , belonging to the research group of Prof. Marcos Borato Viana, of the of the Pediatrics Department of the Universidade Federal de Minas Gerais (UFMG), shows us. The neonatal screening program run by the Nucleus of Actions and Research in Diagnosis at this university has helped to provide a greater understanding of the hemoglobinopathies found in different regions of Brazil - each one with its own ethnical characteristics and diversity - and has highlighted the importance of screening in itself and of correctly identifying other variants that can be confused with Hb S.…”

Hemoglobin Ottawa (HBA2:c.46G>C) and β+ Thalassemia (HBB:c.-138C>T) Detected in an Indian Male by Capillary Zone Electrophoresis

“…Hb Ottawa results from GGT>CGT mutation in codon 15 of either HBA1 [5][6][8][9] or HBA2 5 and has been reported as a mildly unstable Hb variant. 8 Hb Ottawa is not known to have an α-thalassemic effect, so typically the variant is associated with normal hematology in the heterozygote.…”

“…8 Hb Ottawa is not known to have an α-thalassemic effect, so typically the variant is associated with normal hematology in the heterozygote. 1,2,5,6,9,10 However, microcytic red cell indices have previously been described in two cases due to co-inheritance with α-thalassemia-1 6 and β 0 thalassemia. 8 The β + thalassemia mutation (HBB:c.-138C>T) was first described in 1984 11 and has frequently been observed in the American black population.…”