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 spectrin alpha-gene. It carries mutations in exon 40 (alpha(V/41) polymorphism) and intron 45, respectively, and is associated with partial skipping of exon 46. The latter phenomenon is thought to impair the recruitment of alpha-chains by beta-chains, and would eventually account for the 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 anticipated that it would occasionally carry HE determinants. These variants of allele alpha(LELY) will be designated alpha(HE-LELY) alleles. We report two families with the same alpha(HE-LELY) allele. The HE component was the known alpha 28 Arg --> His mutation. This alpha(HE-LELY) allele was investigated within the alpha(HE-LELY)/alpha(LELY) diplotype, a diplotype not described before. Except for the neonatal period, the presentation was mild. In a consistent manner, the alpha(LELY) component in cis of the alpha(HE) mutation counteracted the like component in trans.