SEARCH FOR THE CANDIDATE GENES IN DOMINANT HEREDITARY SPHEROCYTOSIS USING LINKAGE ANALYSIS

Hereditary spherocytosis (HS) is an inherited hemolytic anemia charact erized by the presence of dense spherocytic red cells. In HS patients, red cell membrane protein gel electrophoresis has identified differen t subsets of abnormalities: isolated spectrin deficiency, combined spe ctrin and ankyrin deficiency, band 3 deficiency. To direct the search for the molecular defect in 3 families with dominant HS, we developed microsatellite markers specific for the membrane protein encoding gene s possibly involved in HS (alpha- and beta-spectrin, ankyrin and band 3 genes) and genotyped each family. In 5 families with isolated spectr in deficiency the beta-spectrin gene was designated as candidate. In o ne family with combined spectrin/ankyrin deficiency, only the ankyrin gene was not excluded whereas in the 3 HS families with band 3 deficie ncy, only the band 3 gene was not excluded. This work allowed developm ent of a reliable methodology to search for candidate genes in HS and showed the frequent involvement of the beta-spectrin gene in HS with i solated spectrin deficiency.