Double heterozygosity for the codon beta 39 C-to-T nonsense mutation and a triplicate alpha-globin gene locus can cause "dominantly" inherited beta-thalassemia intermedia.
BACKGROUND
A beta-thalassemia intermedia phenotype can be caused by multiple genotypes.


METHODS
We studied a family where the mother was hematologically normal and both father and daughter had beta-thalassemia intermedia.


RESULTS
Both affected individuals were heterozygous for a codon 39 CAG-to-TAG mutation. They also were heterozygous for a triplicate alpha-globin gene locus (alphaalphaalpha(anti 3.7)).


CONCLUSIONS
This compound heterozygous condition of a beta39 C-to-T mutation and triplicate alpha-globin gene increases alpha:beta-globin chain imbalance and accounts for the presence of beta-thalassemia intermedia. The proband received both an abnormal beta-globin gene and a triplicate alpha-globin locus from her father. Although the phenotype seems to be dominantly inherited, because of independent segregation of the alpha- and beta-globin genes, it is more accurately an example of polygenic inheritance.
Rhodes
S L
SL
VA Medical Center and Department of Medicine, University of Mississippi, Jackson 39216, USA.
Plonczynski
M
M
Harrell
A
A
Li
J
J
Safaya
S
S
Files
J C
JC
Steinberg
M H
MH
D003062:Codon / Q000235:genetics*; D003596:Cytosine / Q000378:metabolism; D005260:Female; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D013941:Thymine / Q000378:metabolism; D017085:alpha-Thalassemia / Q000235:genetics; D017086:beta-Thalassemia / Q000235:genetics*
D003062:Codon; D003596:Cytosine; D005914:Globins; D013941:Thymine