Double Heterozygosity for the Codon β 39 C-to-T Nonsense Mutation and a Triplicate α-Globin Gene Locus Can Cause “Dominantly” Inherited β-Thalassemia Intermedia

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Abstract

Background

A β-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 β-thalassemia intermedia.

Results

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

Conclusions

This compound heterozygous condition of a β39 C-to-T mutation and triplicate α-globin gene increases α:β-globin chain imbalance and accounts for the presence of β-thalassemia intermedia. The proband received both an abnormal β-globin gene and a triplicate α-globin locus from her father. Although the phenotype seems to be dominantly inherited, because of independent segregation of the α- and β-globin genes, it is more accurately an example of polygenic inheritance.

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