Pitfalls in genetic counselling for beta-thalassemia: an individual with 4 different thalassemia mutations.
This paper describes a complex combination of four thalassemia genes (delta(+), beta(0), nondeletion and deletion alpha-thalassemia) in the spouse of a typical high Hb A2 beta-thalassemia carrier presenting for genetic counselling. This complex gene combination resulted in a hematological phenotype, characterized by thalassemia-like red cell indices, normal Hb A2 and Hb F levels and slightly reduced alpha/beta globin chain synthesis ratio, and therefore not indicative for the presence of beta-thalassemia trait. Family studies in combination with alpha-globin gene mapping, haplotype analysis at the beta-globin gene cluster and definition of the beta-thalassemia mutation by oligonucleotide hybridization led us to identify a beta-thalassemia mutation, to define the molecular basis for this phenotype and give the appropriate genetic counselling.
Galanello
R
R
Istituto di Clinica e Biologia dell'Età Evolutiva, Università Studi Cagliari, Sardinia, Italy.
Paglietti
M E
ME
Addis
M
M
Melis
M A
MA
Tuveri
T
T
Furbetta
M
M
Cao
A
A
D005260:Female; D005817:Genetic Counseling; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013789:Thalassemia / Q000235:genetics* / Q000517:prevention & control
D005914:Globins