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.