MUTATION Codon 27 (G->T); GCC(Ala)->TCC(Ser)
 
AMINO ACID REPLACEMENT Ala->Ser (Hb Knossos)
TYPE OF BETA-THAL beta+
MECHANISM Activation of an alternate splicing site in codon 25 resulting in a decreased quantity of normal mRNA 
Gly Gly Glu Ala              
24  25  26  27               
GT  GGT GAG GCC (->TCC = Ser)
    ^
IDENTIFICATION Protein analysis; cloning and amplification of the beta-globin gene; DNA sequencing; dot-blot analysis with allele specific probes
HEMATOLOGY IN HETEROZYGOTE(S) Mild beta-thal phenotype
HEMATOLOGY IN HOMOZYGOTE(S) Thalassemia intermedia
OCCURRENCE In Mediterranean populations; low frequencies
HAPLOTYPE Type I
FOUND IN COMBINATION WITH ABNORMAL HB(S) Hb S; Hb Lepore
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S) Various alleles common in the Mediterranean populations

TABLE A.   Hematological and Hb Composition Data for Four Patients With Hb Knossos [beta27(B9) Ala-> Ser] and a Classical Beta-Thal Heterozygosity
Type of Beta-Thal Hb g/dl MCV fl MCH pg Hb A2 % Hb F %
IVS-I-6, T->C 9.4 86.0 26.1 7.9 3.5
Codon 8, -AA 8.0 77.0 22.5 1.8 39.0
IVS-I-110, G->A 7.7 73.0 19.1 4.5 14.2
IVS-I-1, G->A 9.2 79.0 26.0 1.3 41.3

OTHER INFORMATION None
       
REFERENCES
1. Arous, N., Galacteros, F., Fessas, P., Loukopoulos, D., Blouquit, Y., Komis, G., Sellaye, M., Boussiou, M., and Rosa, J.: FEBS Lett., 147:247, 1983.
2. Orkin, S.H., Antonarakis, S.E., and Loukopoulos, D.: Blood, 64:311, 1984.

This material is from the book A Syllabus of Thalassemia Mutations (1997) by Titus H.J. Huisman, Marianne F.H. Carver, and Erol Baysal, published by The Sickle Cell Anemia Foundation in Augusta, GA, USA. Copyright © 1997 by Titus H.J. Huisman. All rights reserved. Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, microfilming and recording, or by any information storage and retrieval systems, without permission in writing from the Author.