title: Association of the alpha-spectrin R28H mutation with allele alphaLELY and with alphaI/alphaII domain haplotypes in three Brazilian families.
abstract: We have studied three Brazilian kindreds presenting spectrin alpha/74 hereditary elliptocytosis (HE) due to a G-->A substitution, responsible for the R28H mutation. The mutant allele was associated with alphaI domain haplotype 1 (XbaI-/MspI-/PvuII+) in all three families and with two different alphaII domain haplotypes (1/RIT, 4/RVR). This result may reflect that this mutation occurs in a "hot spot" and may have arisen more than once or that a crossing over event may have occurred between the two domains studied. We detected one new haplotype in the alphaI domain (haplotype 3 -XbaI(+)/MspI(-)/PvuII(+)). The mutant allele was associated with the lack of the alphaII domain Alu insertion in all three cases. Allele alphaLELY, detected by PCR and restriction enzyme digestion, was present in the heterozygous form in patient 1 (alphaHE/alphaLELY) and in the homozygous form in patients 2 and 3(alphaHE-LEL/alphaLELY). It was found to be associated with domain haplotypes I (RIT) and 4 (RVR) and with the presence and absence of the Alu insertion. This may have arisen through recombination events, since this polymorphism is located in the alphaIV-alphaV domain junction, which is far distant from the alphaII domain.
authors.affiliation: Center of Hematology and Hemotherapy, Department of Genetics and Evolution, State University of Campinas, SP, Brazil.
authors.forename: D S
authors.initials: DS
authors.lastname: Bassères
authors.forename: S
authors.initials: S
authors.lastname: Bordin
authors.forename: F F
authors.initials: FF
authors.lastname: Costa
authors.forename: S T
authors.initials: ST
authors.lastname: Saad
mesh_terms: D019943:Amino Acid Substitution; D001938:Brazil; D002648:Child; D005260:Female; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D009679:Nuclear Family; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015183:Restriction Mapping; D013049:Spectrin / Q000737:chemistry / Q000235:genetics*
chemical_list: D013049:Spectrin