Beta-thalassemia, HB S-beta-thalassemia and sickle cell anemia among Tunisians.
We analyzed the mutations present in 19 patients with beta-thalassemia major, in 11 patients with Hb S-beta-thalassemia, and the beta S haplotypes of 34 patients with sickle cell anemia. The study included 84 relatives. Dot-blot analysis of amplified DNA with various specific oligonucleotide probes identified 11 different known beta-thalassemia mutations and frameshifts; a new frameshift at codons 25/26 (+T) was detected through sequencing of amplified DNA. The common beta-thalassemia mutations at codon 39 (C----T) and at IVS-I-110 (G----A) were also most prevalent among the Tunisian patients, while the milder T----C mutation at IVS-I-6 was not found. All mutations cause a beta 0-thalassemia or a severe beta + -thalassemia [T----A at -30; IVS-I-5 (G----A); IVS-I-110 (G----A)] which explains the need for regular blood transfusions in the thalassemia major and S-beta-thalassemia patients. Nearly all sickle cell anemia patients carried the beta S mutation on a chromosome with haplotype 19 (or Benin) and all had severe anemia with sickling complications. Identification of the beta S haplotype was through dot-blot analysis with oligonucleotide probes that detect mutations in the G gamma and A gamma promoter sequences, specific for this haplotype.
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
S
S
Fattoum
F
F
Guemira
C
C
Oner
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R
Oner
H W
HW
Li
F
F
Kutlar
T H
TH
Huisman
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D002675:Child, Preschool; D003062:Codon; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D005914:Globins / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D012805:Sickle Cell Trait / Q000150:complications / Q000235:genetics; D013789:Thalassemia / Q000150:complications / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D014416:Tunisia / Q000453:epidemiology
D003062:Codon; D015345:Oligonucleotide Probes; D005914:Globins