103 CLINICAL AND GENETIC HETEROGENEITY OF RECESSIVE FORM OF HEREDITARY SPHEROCYTOSIS

α-spectrin synthesis exceeds s by a factor four (Hanspal, 1987). This suiemeni suggests that α-spectrin deficiency would be evident only in the homozygous slate. Agre (1982, 85) described some cases of recessivcly inherited HS characterized by severe spectrin deficiency and life-threatening hemolysis. Marchcsi (1989) founded in 9 out of 20 of these kindreds an acidic shift of αII domain. More recently Forget (1990) analyzing the genomic DNA of these subjects demonstrated an Ala-Asp (GAT-GCT) substitution at position 972 of α-sp. In order to assess clinical findings of rHS and verily the linkage with α-spccirin gene we studied 11 unrelated kindreds of Italian extraction, characterized by affected propositus with hematologic ally and biochemically normal parents. Two of these had severe HS, whereas the remaining have a clinical picture of typical HS, We examined 3 polymorphic sites (Xbal, PvuII, MspI) founded in linkage disequilibrium with α-sp gene (Hoffman, 1987)(3021-EI cDNA probe was given by courtesy of B.C.Forget). In the informative families rHS is associated with the following liaplotypc X(+), P(-), M(+) in three chromosomes and with ++-, -+- and – in three others. The haplotypc ++ is the most frequent in normal population of our country. This finding suggests the heterogeneity of molecular defect at the α-gene level. Furthermore in two cases the haplotype assignement allows lo the exclusion of α-sp gene involvement. This suggests thai lite α-spectrin gene abnormalities couldn't cause all rHS.