title: Genetic analysis of beta-thalassemia major and beta-thalassemia intermedia in Brazil.
abstract: The development of methodologies to identify the molecular lesions responsible for different types of beta-thalassemia has made it possible to correlate these data with clinical and hematological severity. We examined DNA from 35 patients with beta-thalassemia, residents of the State of São Paulo, Brazil, for some types of genetic modifying factors: beta-thalassemia mutations, the upstream Xmnl GY-globin gene polymorphisms, and alpha-globin gene deletions. Additionally, the beta-like gene cluster haplotypes and the presence of the AYT variant were studied. The following mutations were present in the 70 chromosomes studied: 54.3% codon 39 (C-->T) (beta degree); 18.6% IVS-I-6 (T-->C) (beta+); 18.6% IVS-I-110 (G-->A) (beta+), and 4.3% IVS-I-1 (G-->T) (beta degree). Haplotype II was associated with the nonsense mutation at codon 39, haplotype I with the IVS-I-110 and codon 39 mutations, and haplotypes VI and VII with the IVS-I-6 mutation. The Xmnl polymorphism was detected in three out of 31 patients studied. No alpha-thalassemia was detected among the thalassemia intermedia patients. The AYT variant was present in 87.1% of 31 thalassemia patients and was associated with the codon 39/haplotype II and IVS-I-6/haplotype VI mutations. This is the first study of the Brazilian population that has analyzed the beta-thalassemia mutations and other molecular variants, and has correlated them with the clinical manifestations.
authors.affiliation: Federal University of São Paulo, Brazil.
authors.forename: S F
authors.initials: SF
authors.lastname: Fonseca
authors.forename: J
authors.initials: J
authors.lastname: Kerbauy
authors.forename: C
authors.initials: C
authors.lastname: Escrivao
authors.forename: M S
authors.initials: MS
authors.lastname: Figueiredo
authors.forename: R
authors.initials: R
authors.lastname: Cancado
authors.forename: V R
authors.initials: VR
authors.lastname: Arruda
authors.forename: S T
authors.initials: ST
authors.lastname: Saad
authors.forename: F F
authors.initials: FF
authors.lastname: Costa
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D014644:Genetic Variation; D005914:Globins / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D017354:Point Mutation / Q000235:genetics; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins; C028649:endodeoxyribonuclease XmnI; D015252:Deoxyribonucleases, Type II Site-Specific