title: alpha-thalassaemia as a result of a novel splice donor site mutation of the alpha1-globin gene.
abstract: We describe the characterization of an alpha+-thalassaemia determinant as a result of a transition of G-->A of the donor splice consensus site sequence of the first intron of the alpha1-globin gene (alpha1IVS I-1). The mutation was found in combination with the South-East Asian alpha0-thalassaemia deletion in an haemoglobin (Hb)H patient and her sister, both of Thai origin. Sequencing of the abnormally spliced mRNA product revealed the presence of a cryptic splice site in exon 1 of the alpha1-globin gene. No normally spliced alpha1mRNA was detected. The abnormally spliced mRNA product from the alpha1-gene carrying the mutation does not lead to functional protein and causes a mild HbH-disease phenotype when in combination with the deletion type alpha0-thalassaemia.
authors.affiliation: Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands. keesh@LUMC.nl
authors.forename: C L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: C
authors.initials: C
authors.lastname: Beijer
authors.forename: P
authors.initials: P
authors.lastname: van Delft
authors.forename: R
authors.initials: R
authors.lastname: Zanardini
authors.forename: L F
authors.initials: LF
authors.lastname: Bernini
authors.forename: P C
authors.initials: PC
authors.lastname: Giordano
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D002675:Child, Preschool; D004587:Electrophoresis, Agar Gel; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017085:alpha-Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins