title: A novel polyadenylation signal mutation in the alpha 2-globin gene causing alpha thalassaemia.
abstract: 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.
authors.affiliation: Department of Human Genetics, Leiden University, The Netherlands.
authors.forename: C L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: M
authors.initials: M
authors.lastname: Losekoot
authors.forename: H
authors.initials: H
authors.lastname: Haak
authors.forename: G A
authors.initials: GA
authors.lastname: Heister
authors.forename: P C
authors.initials: PC
authors.lastname: Giordano
authors.forename: L F
authors.initials: LF
authors.lastname: Bernini
mesh_terms: 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*
chemical_list: D011061:Poly A; D005914:Globins