A molecular study of heterozygous protein 4.1 deficiency in hereditary elliptocytosis

Genomic DNA from five kindreds and two individuals with hereditary elliptocytosis [HE(4.1+)] and a partial deficiency of protein 4.1 [HE(4.1+)] was extracted and probed with a cDNA for protein 4.1. When using a fragment of the cDNA that encompassed the coding region of the gene, two restriction fragment length polymorphisms segregating with protein 4.1 deficiency were found in one kindred when using the enzymes BgIII and PvuII but were not seen in the other HE(4.1+) subjects or in 20 random control individuals. DNA digested with three other enzymes (HindIII, EcoRI, TaqI) produced restriction patterns similar to controls. The unique BgIII and PvuII polymorphisms probably reflect a rearrangement of the coding region of the protein 4.1 gene as the underlying cause of the partial protein 4.1 deficiency in this family. A less likely possibility is that these polymorphisms represent coincidental single base changes unrelated to the primary gene defect.