ClinVar

In a 51-year-old Spanish man with inclusion body beta-thalassemia (603902), Ropero et al. (2005) identified a heterozygous 11-basepair deletion in exon 3 of the HBB gene by direct sequencing. The deletion from codon 131 to codon 134 (-CAGAAAGTGGT) was predicted to produce a frameshift and synthesis of an abnormal and likely unstable beta-chain variant of 134 amino acids instead of the normal 146 amino acids. Inheritance could not be determined because the parents were deceased. The patient was diagnosed with beta-thalassemia in adulthood with marked siderosis, slight microcytic anemia that never needed transfusion, moderate hemolysis, subclinical jaundice, painful splenomegaly, and hepatomegaly. The patient was also homozygous for the H63D substitution in the HFE gene (613609.0002); the authors noted that the HFE variant increases the probability of developing iron overload when it is associated with beta-thalassemia, and suggested that it could contribute to siderosis.