Molecular basis of Sp alpha I/65 hereditary elliptocytosis in North Africa:
insertion of a TTG triplet between codons 147 and 149 in the alpha-spectrin
gene from five unrelated families
AF Roux, F Morle, D Guetarni, P Colonna, K Sahr, BG Forget, J Delaunay and J Godet
CNRS UMR 0004, Laboratoire de Biologie Cellulaire, Villeurbanne, France.
Hereditary elliptocytosis in North Africa is frequently associated with the
alpha I/65 spectrin variant, characterized by an abnormal alpha I 65-kD
instead of the normal alpha I 80-kD peptide following limited trypsin
digestion of whole spectrin. A similar variant (although it yielded a 68-kD
fragment) has been shown recently, in two black patients, to result from
the insertion of a leucyl residue at position 148 (Marchesi et al: J Clin
Invest 80:191, 1987). In order to determine if the underlying molecular
defect was the same in North Africans and blacks (who originate from both
sides of the Sahara Desert), we performed analysis directly at the DNA
level. Starting from the DNA of an Algerian alpha I/65 heterozygote in whom
the mutation was associated with identifiable RFLPs, we cloned and
sequenced the alpha-spectrin gene region, which includes the mutation. We
thus identified an extra leucine codon (TTG) between codons 147 and 149,
the coding sequence becoming CAG TTG TTG CTG instead of CAG TTG CTG. We
then used the polymerase chain reaction (PCR) method and dot-blot
hybridization of the amplified DNA with mutant and normal allele-specific
oligonucleotides to screen the DNA from four other unrelated North African
subjects with Sp alpha I/65 hereditary elliptocytosis. In all families we
studied, these subjects were heterozygous for the TTG insertion. These
results demonstrate that Sp alpha I/65 hereditary elliptocytosis has the
same molecular basis in North Africans and blacks.
Volume 73,
Issue 8,
pp. 2196-2201,
06/01/1989
Copyright © 1989 by The American Society of Hematology
