Frequent de novo monoallelic expression of β‐spectrin gene (SPTB) in children with hereditary spherocytosis and isolated spectrin deficiency

This report represents an attempt to define the rate of β‐spectrin de novo mutations affecting mRNA accumulation in patients with hereditary spherocytosis (HS). 19 HS children with haematologically normal parents and varying degrees of spectrin deficiency were studied. 13 of the 19 cases who were heterozygous at the genomic level for polymorphisms in the β‐spectrin coding region were further studied. However, in an analysis of reverse‐transcripted amplified cDNA from the regions of the polymorphisms, seven patients appeared to be homozygous, suggesting the occurrence of de novo mutational events affecting expression of one β‐spectrin allele. We conclude that in HS patients with isolated spectrin reduction and normal parents the apparently recessive pattern of inheritance may frequently be associated with de novo monoallelic expression of β‐spectrin.