Clinical and genetic heterogeneity in black patients with homozygous β-thalassemia from the Southeastern United States

J. M. Gonzalez-Redondo, T. A. Stoming, K. D. Lanclos, Y. C. Gu, A. Kutlar, T. Nakatsuji, B. Deng, I. S. Han, V. C. McKie, T. H.J. Huisman

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1007-1014
Number of pages8
JournalBlood
Volume72
Issue number3
StatePublished - Jan 1 1988

Fingerprint

Southeastern United States
Thalassemia
Genetic Heterogeneity
Fetal Hemoglobin
Chromosomes
Substitution reactions
Mutation
Codon
Globins
Nucleotides
Haplotypes
Genes
Hemoglobin A2
Taq Polymerase
Cloning
DNA
Oligonucleotides
Amplification
Exons
Chromosomes, Human, Pair 21

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Gonzalez-Redondo, J. M., Stoming, T. A., Lanclos, K. D., Gu, Y. C., Kutlar, A., Nakatsuji, T., ... Huisman, T. H. J. (1988). Clinical and genetic heterogeneity in black patients with homozygous β-thalassemia from the Southeastern United States. Blood, 72(3), 1007-1014.

Clinical and genetic heterogeneity in black patients with homozygous β-thalassemia from the Southeastern United States. / Gonzalez-Redondo, J. M.; Stoming, T. A.; Lanclos, K. D.; Gu, Y. C.; Kutlar, A.; Nakatsuji, T.; Deng, B.; Han, I. S.; McKie, V. C.; Huisman, T. H.J.

In: Blood, Vol. 72, No. 3, 01.01.1988, p. 1007-1014.

Research output: Contribution to journalArticle

Gonzalez-Redondo, JM, Stoming, TA, Lanclos, KD, Gu, YC, Kutlar, A, Nakatsuji, T, Deng, B, Han, IS, McKie, VC & Huisman, THJ 1988, 'Clinical and genetic heterogeneity in black patients with homozygous β-thalassemia from the Southeastern United States', Blood, vol. 72, no. 3, pp. 1007-1014.
Gonzalez-Redondo JM, Stoming TA, Lanclos KD, Gu YC, Kutlar A, Nakatsuji T et al. Clinical and genetic heterogeneity in black patients with homozygous β-thalassemia from the Southeastern United States. Blood. 1988 Jan 1;72(3):1007-1014.
Gonzalez-Redondo, J. M. ; Stoming, T. A. ; Lanclos, K. D. ; Gu, Y. C. ; Kutlar, A. ; Nakatsuji, T. ; Deng, B. ; Han, I. S. ; McKie, V. C. ; Huisman, T. H.J. / Clinical and genetic heterogeneity in black patients with homozygous β-thalassemia from the Southeastern United States. In: Blood. 1988 ; Vol. 72, No. 3. pp. 1007-1014.
@article{510f48b5520c48ddb9e93bef51f89dc0,
title = "Clinical and genetic heterogeneity in black patients with homozygous β-thalassemia from the Southeastern United States",
abstract = "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.",
author = "Gonzalez-Redondo, {J. M.} and Stoming, {T. A.} and Lanclos, {K. D.} and Gu, {Y. C.} and A. Kutlar and T. Nakatsuji and B. Deng and Han, {I. S.} and McKie, {V. C.} and Huisman, {T. H.J.}",
year = "1988",
month = "1",
day = "1",
language = "English (US)",
volume = "72",
pages = "1007--1014",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

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 - 1988/1/1

Y1 - 1988/1/1

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.

UR - http://www.scopus.com/inward/record.url?scp=0023782895&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023782895&partnerID=8YFLogxK

M3 - Article

C2 - 2458145

AN - SCOPUS:0023782895

VL - 72

SP - 1007

EP - 1014

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -