beta-Spectrin S-ta Barbara: a novel frameshift mutation in hereditary spherocytosis associated with detectable levels of mRNA and a germ cell line mosaicism

Hereditary spherocytosis (HS) is a common inherited anaemia characterized b y the presence of spherocytic red cells and by a heterogeneous nature in te rms of its clinical presentation, molecular basis and inheritance. Defects in several membrane protein genes have been involved in the pathogenesis of HS, including defects in the beta -spectrin gene. We detected a novel fram eshift mutation in the beta -spectrin gene, a C deletion at codon 638, in a patient presenting with HS and spectrin deficiency. The mutant protein was not detected in the membrane or in other cellular compartments, but detect able levels of mutant mRNA were found in the patient. Interestingly, this m utation was not present in the patient's parents, suggesting a genetic mosa icism, especially as the patient has an affected brother with the same mole cular defect. We analysed DNA from different tissues of the parents and the mutation was absent from all tissues analysed. This mutation seems to be c onfined to the germ cell lineage of the patient's mother and must present a mosaic pattern in these cells as the patient also has unaffected siblings.