title: Molecular characterization of alpha-thalassemia determinants, beta-thalassemia alleles, and beta S haplotypes among Kuwaiti Arabs.
abstract: Using amplification, allele-specific oligonucleotide (ASO) hybridization and DNA sequencing we have documented the molecular basis of 64 alpha- and 123 beta-thalassemia (thal) chromosomes, and the haplotypes of 18 beta S chromosomes from patients followed in three hospitals in Kuwait. Of the 30 chromosomes from 15 patients with Hb H disease, 26 (86.7%) carried the polyadenylation (poly A) signal mutation (AATAAA-->AATAAG) in the alpha 2-globin gene, 3 (10%) had the -alpha (3.7 kb) deletion, and 1 (3.3%) had the pentanucleotide deletion in the 5' IVS-I splice junction (alpha-5nt alpha). As many as 12 different beta-thal mutations were identified; 6 Mediterranean alleles [IVS-II-1 (G-->A), IVS-I-6 (T-->C), codon (CD) 39 (C-->T), IVS-I-110 (G-->A), CD 8 (-AA), and IVS-I-1 (G-->A)] were present in 79 (64.2%) of the chromosomes tested. Four East Indian alleles [IVS-I-5 (G-->C), IVS-I 3' end -25 nt deletion, CDs 8/9 (+G), and 619-bp deletion] were found in 31 (25%), and the two Kurdish/Iranian alleles [CD 44 (-C) and CDs 36/37 (-T)] were found in 13 (10.6%) chromosomes. Fourteen beta S chromosomes carried haplotype No. 31 (Saudi Arabia/India); 3 had haplotype No. 19 (Benin), and 1 was a hybrid with haplotype No. 31-specific characteristics in the locus control region hypersensitive site-2 (LCR-HS-2), and haplotype No. 19-specific mutations in the 5' flanking region of the G gamma-promoter. The patient homozygous for haplotype No. 19 was a Jordanian, while the others were Kuwaiti Arabs. The latter appear to be fairly homogeneous in terms of the prevalent alpha-thal determinants and beta S-haplotypes, but there is considerable heterogeneity of their beta-thal alleles. This has implications for genetic counseling and prenatal diagnosis programs.
authors.affiliation: Department of Paediatrics, Faculty of Medicine, Kuwait University.
authors.forename: A D
authors.initials: AD
authors.lastname: Adekile
authors.forename: L H
authors.initials: LH
authors.lastname: Gu
authors.forename: E
authors.initials: E
authors.lastname: Baysal
authors.forename: M Z
authors.initials: MZ
authors.lastname: Haider
authors.forename: L
authors.initials: L
authors.lastname: al-Fuzae
authors.forename: K C
authors.initials: KC
authors.lastname: Aboobacker
authors.forename: A
authors.initials: A
authors.lastname: al-Rashied
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics*; D018643:Arab World; D001483:Base Sequence; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D007730:Kuwait / Q000208:ethnology; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017085:alpha-Thalassemia / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins