Molecular characterization of a normal Hb A2 beta-thalassaemia determinant in a Sardinian family.
In this study we have carried out haplotype analysis at the beta-globin gene cluster and defined the beta-thalassaemia mutations in a large Sardinian family, ascertained through a proband with thalassaemia major, in which several members were carriers of a beta-thalassaemia allele characterized by microcytosis, hypochromia and normal Hb A2 levels (type 2 normal Hb A2 heterozygous beta-thalassemia). The proband was a compound heterozygote for the beta zero 39 and the beta + IVS-2, nt 745 mutations and all the beta-thalassaemia heterozygotes with normal Hb A2 showed the beta + IVS-2, nt 745 mutation, always associated with haplotype VII. Because of the consistent association of a specific beta-thalassaemia mutation and normal Hb A2 levels, we postulate that this beta-thalassaemia chromosome carries a delta gene (delta-thalassaemia) which is unable to increase the delta-globin output in response to beta-thalassaemia.
Oggiano
L
L
Istituto di Clinica Medica Generale e Terapia Medica, Università degli Studi di Sassari, Italy.
Pirastu
M
M
Moi
P
P
Longinotti
M
M
Perseu
L
L
Cao
A
A
D002675:Child, Preschool; D002874:Chromosome Mapping; D005260:Female; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006441:Hemoglobin A / Q000235:genetics*; D006443:Hemoglobin A2 / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation; D010375:Pedigree; D013789:Thalassemia / Q000235:genetics*
D005914:Globins; D006441:Hemoglobin A; D006443:Hemoglobin A2