title: Different impacts of alleles alphaLEPRA and alphaLELY as assessed versus a novel, virtually null allele of the SPTA1 gene in trans.
abstract: The family of two siblings with severe hereditary spherocytosis was investigated. The decrease was evident on both the alpha- and the beta-chains. The parents were haematologically normal. The mother was heterozygous for the low-expression polymorphic allele alphaLEPRA. The father was heterozygous for a novel combination in which one allele showed the alpha-spectrin low expression polymorphic allele alphaLELY, while his other allele showed the alphaLELY polymorphism in cis with a G-->A substitution, named Bicêtre, found at the extreme 3' end of exon 51. This combination was designated alpha(LELY-Bicêtre). The children were compound heterozygotes for alleles alphaLEPRA and alpha(LELY-Bicêtre). Reverse transcription polymerase chain reaction detected only trace amounts of the mRNA coding for alpha(LELY-Bicêtre). Mutation is therefore an essentially null mutation with no functional protein product. The lack of disease in the alphaLELY/(LELY-Bicêtre) father compared with the marked haemolysis in the alphaLEPRA/alpha(LELY-Bicêtre) children showed that expression of allele alphaLELY is not low enough to expose null alpha-spectrin alleles on the other chromosome. Quantitative estimations from these findings suggest that, to evoke spherocytosis, it is necessary that alpha-spectrin expression must be reduced to less than 25% of normal, while a reduction to 8% is sufficient.
authors.affiliation: Laboratoire d'Hématologie, d'Immunologie et de Cytogénétique, Hopital de Bicetre, Le Kremlin-Bicetre, France. jean.delaunay@bct.ap-hop-paris.fr
authors.forename: J
authors.initials: J
authors.lastname: Delaunay
authors.forename: V
authors.initials: V
authors.lastname: Nouyrigat
authors.forename: A
authors.initials: A
authors.lastname: Proust
authors.forename: P-O
authors.initials: PO
authors.lastname: Schischmanoff
authors.forename: T
authors.initials: T
authors.lastname: Cynober
authors.forename: J
authors.initials: J
authors.lastname: Yvart
authors.forename: C
authors.initials: C
authors.lastname: Gaillard
authors.forename: O
authors.initials: O
authors.lastname: Danos
authors.forename: G
authors.initials: G
authors.lastname: Tchernia
mesh_terms: D000483:Alleles; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D013049:Spectrin / Q000235:genetics*; D013103:Spherocytosis, Hereditary / Q000097:blood / Q000235:genetics*
chemical_list: D013049:Spectrin