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Identification of four novel delta-globin gene mutations in Greek Cypriots
using polymerase chain reaction and automated fluorescence- based DNA
sequence analysis
P Trifillis, P Ioannou, E Schwartz and S Surrey
Children's Hospital of Philadelphia, Department of Pediatrics, University
of Pennsylvania School of Medicine.
The molecular basis of most beta-thalassemia syndromes has been defined,
while the spectrum of mutations causing delta-thalassemia is not well
characterized. In an attempt to identify such mutations, the region
encompassing the delta-globin gene from three Greek Cypriot families
suspected of having delta-thalassemia was amplified by polymerase chain
reaction (PCR), and DNA sequence determined using an automated
fluorescence-based sequencer. Four novel mutations were identified: a
G----T change at codon 27 that results in an alanine to serine change; a
C----T change at codon 116 converting arginine to cysteine; a T----C change
at codon 141 converting leucine to proline; and an AG----GG change at the
consensus 3'-acceptor site in IVS-2. While the latter is clearly a
thalassemic mutation, the low hemoglobin A2 in the first three may be due
to either decreased production or instability of the altered delta-globin
chain. All four mutations may be detected by PCR amplification of genomic
DNA followed by restriction enzyme digestion. Two mutations abolish
restriction sites while two create new cleavage sites. Screening for
molecular defects that cause delta-thalassemia or unstable delta-globin by
PCR amplification and restriction enzyme digestion will lead to correct
diagnosis of beta/delta-thalassemia compound heterozygotes and improved
genetic counseling.
Volume 78,
Issue 12,
pp. 3298-3305,
12/15/1991
Copyright © 1991 by The American Society of Hematology
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P. Trifillis, K. Adachi, T. Yamaguchi, E. Schwartz, and S. Surrey
Expression Studies of delta -Globin Gene Alleles Associated with Reduced Hemoglobin A2 Levels in Greek Cypriots
J. Biol. Chem.,
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K. Adachi, J. Pang, L. R. Reddy, L. E. Bradley, Q. Chen, P. Trifillis, E. Schwartz, and S. Surrey
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L. R. Reddy, K. S. Reddy, S. Surrey, and K. Adachi
Role of Hydrophobic Amino Acids at beta 85 and beta 88 in Stabilizing F Helix Conformation of Hemoglobin S
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P Fortina, G Dotti, R Conant, G Monokian, T Parrella, W Hitchcock, E Rappaport, E Schwartz, and S Surrey
Detection of the most common mutations causing beta-thalassemia in Mediterraneans using a multiplex amplification refractory mutation system (MARMS).
Genome Res.,
November 1, 1992;
2(2):
163 - 166.
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