TY - JOUR
T1 - Clinical and genetic heterogeneity in black patients with homozygous β-thalassemia from the Southeastern United States
AU - Gonzalez-Redondo, J. M.
AU - Stoming, T. A.
AU - Lanclos, K. D.
AU - Gu, Y. C.
AU - Kutlar, A.
AU - Nakatsuji, T.
AU - Deng, B.
AU - Han, I. S.
AU - McKie, V. C.
AU - Huisman, T. H.J.
PY - 1988
Y1 - 1988
N2 - The presence of various substitutions and deletions resulting in β-thalassemia was studied in 19 black patients with homozygous β-thalassemia and in numerous relatives; all patients were from Georgia, South Carolina, and Alabama. Methodology included gene mapping, amplification of genomic DNA with Taq polymerase, identification of known nucleotide substitutions or a single nucleotide deletion through hybridization with synthetic oligonucleotides, cloning and sequencing of a β-globin gene, and sequencing of amplified genomic DNA. Of the 38 chromosomes tested, 21 (55%) had the A → G substitution at nt -29, eight (21%) had the C → T substitution at nt -88, three (8%) had the substitution at codon 24, while one each of the following abnormalities were also detected frameshift at codon 6, a C → A mutation at nt 848 of the βIVS-II (new), an A → T mutation at codon 61 (new), a deletion of 1.35 kilobases including the 5' end of β, a (G)γ((A)γδβ)°-thalassemia, and one thalassemia determinant that remained unidentified. The C → A mutation at nt 848 of IVS-II occurred at a position 3 nucleotides 5' to the third exon, adjacent to the invariant Ag dinucleotide of the acceptor sequence. The A → T mutation in codon 61 (AAG → TAG) resulted in the creation of a stop codon and thus in ̄°-thalassemia. The various mutations occurred on chromosomes with different haplotypes; however, chromosomes with a specific mutation but with different haplotypes belonged to one specific framework, which suggested that crossovers were responsible for these different types. Hemoglobin (Hb) F levels wre generally high (55% to 75% with 98.5% in one patient with β°/β°); a few patients with specific haplotypes and an α-thalassemia-2 heterozygosity had a lower Hb F level. The (G)γ in the Hb F was consistently high when the C → T mutation occurred at nt -158 to the Cap site of the (G)γ-globin gene; seven patients with +/+ at this site had an average (G)γ of 73.8%, eight patients with +/- had 64.8%, and one patient with -/- had 34.2%. Variations in hematologic values and in Hb F, (G)γ, and Hb A2 levels of relatives with a β-thalassemia heterozygosity depended to some extent on the types of mutations or deletions and on the haplotypes of the chromosomes with the β-thalassemia determinant.
AB - The presence of various substitutions and deletions resulting in β-thalassemia was studied in 19 black patients with homozygous β-thalassemia and in numerous relatives; all patients were from Georgia, South Carolina, and Alabama. Methodology included gene mapping, amplification of genomic DNA with Taq polymerase, identification of known nucleotide substitutions or a single nucleotide deletion through hybridization with synthetic oligonucleotides, cloning and sequencing of a β-globin gene, and sequencing of amplified genomic DNA. Of the 38 chromosomes tested, 21 (55%) had the A → G substitution at nt -29, eight (21%) had the C → T substitution at nt -88, three (8%) had the substitution at codon 24, while one each of the following abnormalities were also detected frameshift at codon 6, a C → A mutation at nt 848 of the βIVS-II (new), an A → T mutation at codon 61 (new), a deletion of 1.35 kilobases including the 5' end of β, a (G)γ((A)γδβ)°-thalassemia, and one thalassemia determinant that remained unidentified. The C → A mutation at nt 848 of IVS-II occurred at a position 3 nucleotides 5' to the third exon, adjacent to the invariant Ag dinucleotide of the acceptor sequence. The A → T mutation in codon 61 (AAG → TAG) resulted in the creation of a stop codon and thus in ̄°-thalassemia. The various mutations occurred on chromosomes with different haplotypes; however, chromosomes with a specific mutation but with different haplotypes belonged to one specific framework, which suggested that crossovers were responsible for these different types. Hemoglobin (Hb) F levels wre generally high (55% to 75% with 98.5% in one patient with β°/β°); a few patients with specific haplotypes and an α-thalassemia-2 heterozygosity had a lower Hb F level. The (G)γ in the Hb F was consistently high when the C → T mutation occurred at nt -158 to the Cap site of the (G)γ-globin gene; seven patients with +/+ at this site had an average (G)γ of 73.8%, eight patients with +/- had 64.8%, and one patient with -/- had 34.2%. Variations in hematologic values and in Hb F, (G)γ, and Hb A2 levels of relatives with a β-thalassemia heterozygosity depended to some extent on the types of mutations or deletions and on the haplotypes of the chromosomes with the β-thalassemia determinant.
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U2 - 10.1182/blood.v72.3.1007.1007
DO - 10.1182/blood.v72.3.1007.1007
M3 - Article
C2 - 2458145
AN - SCOPUS:0023782895
SN - 0006-4971
VL - 72
SP - 1007
EP - 1014
JO - Blood
JF - Blood
IS - 3
ER -