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P Moi, E Paglietti, A Sanna, C Brancati, A Tagarelli, R Galanello, A Cao and M Pirastu
Ospedale Regionale per le Microcitemie, Cagliari, Italy.
In this study, we used cloning and sequence analysis to define the
molecular defect in two delta-thalassemia genes, one associated with
reduced output of delta-globin chains (delta +thal) from a Sardinian and
the other with a complete suppression of delta-chain production from the
affected locus (delta zerp thal) from a Southern Italian. Sequence analysis
of the delta +thal gene showed a G----T substitution at the first
nucleotide of codon 27 (delta +27) which produces an amino acid change
(Ala----Ser) and presumably activates a cryptic splice site located at this
position. Therefore, only a fraction of the transcript is processed from
this site, as indicated by the clinical phenotype of delta +thal. DNA
sequencing of the delta zero thal gene revealed a T---- C substitution at
position 1 of IVS-1, which abolishes the splicing at this site and thus
leads to complete deficiency of normal mRNA explaining the clinical
phenotype of delta zero thal. Oligonucleotide analysis was used to confirm
the coinheritance of the delta +27 mutation in a group of Sardinians with
thalassemia like phenotype and normal HbA2 level who, on the basis of
genetic criteria, were supposed to be double heterozygous for
delta-thalassemia and beta-thalassemia. The definition of delta-thalassemia
defects in each high-risk area facilitates identification of double
heterozygotes for delta- and beta- thalassemia by DNA analysis and may thus
improve genetic counseling.
This article has been cited by other articles:
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| Copyright © 1988 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
