A VARIANT OF SPECTRIN LOW-EXPRESSION ALLELE ALPHA(LELY) CARRYING A HEREDITARY ELLIPTOCYTOSIS MUTATION IN CODON-28

Allele alpha(LELY) is a low-expression allele of the erythroid spectri n alpha-gene. It carries mutations in exon 40 (alpha(V/41) polymorphis m) and intron 45, respectively, and is associated with partial skippin g of exon 46. The latter phenomenon is thought to impair the recruitme nt of alpha-chains by beta-chains, and would eventually account for th e low-expression character. When it occurs in trans to an alpha-allele responsible for hereditary elliptocytosis (alpha(HE) allele; alpha(HE )/alpha(LELY) diplotype), allele alpha(LELY) enhances the severity of elliptocytosis. Because allele alpha(LELY) is widespread, we anticipat ed that it would occasionally carry HE determinants. These variants of allele alpha(LELY) will be designated alpha(HE-LELY) alleles. We repo rt two families with the same alpha(HE-LELY) allele. The HE component was the known alpha 28 Arg --> His mutation. This alpha(HE-LELY) allel e was investigated within the alpha(HE-LELY)/alpha(LELY) diplotype, a diplotype not described before. Except for the neonatal period, the pr esentation was mild. In a consistent manner, the alpha(LELY) component in cis of the alpha(HE) mutation counteracted the like component in t rans.