Molecular characterization of beta-thalassemia in Syria.
This study concerns the determination of beta-thalassemia alleles and other hemoglobin variants in 82 patients from Syria. We have characterized 146 chromosomes and found 17 different beta-thalassemia mutations, and one beta-globin chain variant that gives rise to the abnormal Hb S. The eight most common beta-thalassemia mutations were the IVS-I-110 (G-->A), IVS-I-1 (G-->A), codon 5 (-CT), -30 (T-->A), codon 39 (C-->T), IVS-I-6 (T-->C), IVS-II-1 (G-->A), and codon 15 (TGG-->TAG). These mutations accounted for almost 75% of the total beta-thalassemia chromosomes. We identified 34 different genotypes with a high level of homozygosity. The various beta-thalassemia mutations were characterized using gene amplification with specific oligonucleotide primers, restriction enzyme analysis, denaturing gradient gel electrophoresis and direct sequencing. By combining these three approaches we were able to detect mutations in almost 90% of the chromosomes studied. Our findings provide a sound foundation on which to base a preventive program for thalassemia and we believe that the data that we present will facilitate the improvement of medical services such as carrier screening, genetic counseling, and prenatal diagnosis. Furthermore a detailed knowledge of the molecular pathology of beta-thalassemia will strongly improve the prenatal diagnosis services in Syria.
Kyriacou
K
K
The Thalassaemia Laboratory, The Cyprus Institute of Neurology and Genetics Nicosia.
Al Quobaili
F
F
Pavlou
E
E
Christopoulos
G
G
Ioannou
P
P
Kleanthous
M
M
D000293:Adolescent; D000483:Alleles; D019943:Amino Acid Substitution; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D003535:Cyprus / Q000453:epidemiology / Q000208:ethnology; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D005787:Gene Frequency; D005838:Genotype; D006455:Hemoglobins, Abnormal / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008877:Middle East / Q000453:epidemiology / Q000208:ethnology; D020125:Mutation, Missense; D017354:Point Mutation; D013156:Splenectomy; D013593:Syria / Q000453:epidemiology / Q000208:ethnology; D017086:beta-Thalassemia / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*
D006455:Hemoglobins, Abnormal