alpha-Thalassaemia due to a single codon deletion in the alpha1-globin gene. Computational structural analysis of the new alpha-chain variant. Mutations in brief no. 132. Online.
A new unstable alpha-globin chain associated with alpha-thalassemia phenotype has been found in a Spanish patient. Molecular analysis of the alpha-globin gene complex using PCR and non-radioactive single-strand conformation analysis, allowed to identify a new mutation in the second exon of the alpha-globin gene. Direct sequencing of the abnormal fragment revealed a 3 bp deletion, which led to the loss of a single codon corresponding to a Lys (K) residue at position 60 or 61 DK60 or DK61. Theoretical structural analysis, performed by computational methods, indicated that the loss of an amino acid residue at this position disturbed the contact region between the B and E-helices, affecting the overall stability of the molecule. Therefore, the DK60 and DK61 results in a structurally abnormal alpha-globin chain, not previously described, named Hb Clinic, which leads to the alpha-thalassemia phenotype in the heterozygote patient. No abnormal hemoglobin was detected by standard electrophoretic procedures, suggesting that this alpha-globin chain variant is so unstable that it may be catabolized immediately after its synthesis. This mutation was confirmed by PCR using an allele specific primer.
Ayala
S
S
Hematology Laboratory Department, Hospital Clínic i Provincial, Faculty of Medicine, University of Barcelona, Spain.
Colomer
D
D
Gelpí
J L
JL
Corrons
J L
JL
D003062:Codon / Q000235:genetics*; D019295:Computational Biology; D005914:Globins / Q000235:genetics*; D006801:Humans; D017384:Sequence Deletion / Q000235:genetics*; D013030:Spain; D017085:alpha-Thalassemia / Q000235:genetics*
D003062:Codon; D005914:Globins