beta-Spectrin Sao Paulo(II), a novel frameshift mutation of the beta-spectrin gene associated with hereditary spherocytosis and instability of the mutant mRNA

Abstract

Hereditary spherocytosis (HS) is a common inherited anemia characterized by the presence of spherocytic red cells. Defects in several membrane protein genes have been involved in the pathogenesis of HS. beta-Spectrin-related HS seems to be common. We report here a new mutation in the beta-spectrin gene coding region in a patient with hereditary spherocytosis. The patient presented acanthocytosis and spectrin deficiency and, at the DNA level, a novel frameshift mutation leading to HS, i.e., a C deletion at codon 1392 (beta-spectrin Sao Paulo(II)), exon 20. The mRNA encoding beta-spectrin Sao Paulo(II) was very unstable and the mutant protein was not detected in the membrane or in other cellular compartments. It is interesting to note that frameshift mutations of the beta-spectrin gene at the 3' end allow the insertion of the mutant protein in the red cell membrane, leading to a defect in the auto-association of the spectrin dinners and consequent elliptocytosis. On the other hand, beta-spectrin Sao Paulo(II) protein was absent in the red cell membrane, leading to spectrin deficiency, HS and the presence of acanthocytes.