title: 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.
abstract: 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.
authors.affiliation: VA Medical Center and Department of Medicine, University of Mississippi, Jackson 39216, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Rhodes
authors.forename: M
authors.initials: M
authors.lastname: Plonczynski
authors.forename: A
authors.initials: A
authors.lastname: Harrell
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Safaya
authors.forename: J C
authors.initials: JC
authors.lastname: Files
authors.forename: M H
authors.initials: MH
authors.lastname: Steinberg
mesh_terms: 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*
chemical_list: D003062:Codon; D003596:Cytosine; D005914:Globins; D013941:Thymine