A novel polyadenylation signal mutation in the alpha 2-globin gene causing alpha thalassaemia.
In a family of Indian origin we have identified a deletion of two bases at the polyadenylation signal sequence of the alpha 2-globin gene (AATAAA-->AATA). Three individuals heterozygous for this mutation display an alpha o-thalassaemia-like phenotype. Single-stranded conformation analysis and automatic sequencing showed no additional mutations in either alpha 1- or alpha 2-globin genes. A previously described polyadenylation sequence mutation (AATAAA-->AATAAG), alpha TSaudi alpha, causes HbH disease in homozygotes. In this study the patients heterozygous for the AATA(-AA) mutation show a similar phenotype observed in the alpha TSaudi alpha heterozygotes. This confirms the observation that the inefficient transcriptional termination due to mutations of the polyadenylation sequence of the alpha 2-gene might interfere with the alpha 1-gene expression.
Harteveld
C L
CL
Department of Human Genetics, Leiden University, The Netherlands.
Losekoot
M
M
Haak
H
H
Heister
G A
GA
Giordano
P C
PC
Bernini
L F
LF
D001483:Base Sequence; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010375:Pedigree; D011061:Poly A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D017085:alpha-Thalassemia / Q000097:blood / Q000235:genetics*
D011061:Poly A; D005914:Globins