title: Heterozygosity for the IVS-I-5 (G-->C) mutation with a G-->A change at codon 18 (Val-->Met; Hb Baden) in cis and a T-->G mutation at codon 126 (Val-->Gly; Hb Dhonburi) in trans resulting in a thalassemia intermedia.
abstract: We have analyzed the hemoglobins of a young German patient with beta-thalassemia intermedia and of his immediate family and included in these studies an evaluation of possible nucleotide changes in the beta-globin genes through sequencing of amplified DNA. One chromosome of the propositus and one of his father's carried the GTG-->GGG mutation at codon 126 leading to the synthesis of Hb Dhonburi or alpha 2 beta (2)126(H4)Val-->Gly; this variant is slightly unstable and is associated with mild thalassemic features. His second chromosome and one of his mother's had the common IVS-I-5 (G-->C) mutation that leads to a rather severe beta(+)-thalassemia and the GTG-->ATG mutation at codon 18, resulting in the replacement of a valine residue by a methionine residue. This newly discovered beta-chain variant, named Hb Baden, was present for only 2-3% in both the patient and his mother. This low amount results from a decreased splicing of RNA at the donor splice-site of the first intron that is nearly completely deactivated by the IVS-I-5 (G-->C) thalassemic mutation. The chromosome with the codon 18 (GTG-->ATG) and the IVS-I-5 (G-->C) mutations has thus far been found only in this German family; analysis of 51 chromosomes from patients with the IVS-I-5 (G-->C) mutation living in different countries failed to detect the codon 18 (GTG-->ATG) change.
authors: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
authors: V
authors: V
authors: Divoky
authors: E
authors: E
authors: Bissé
authors: J B
authors: JB
authors: Wilson
authors: L H
authors: LH
authors: Gu
authors: H
authors: H
authors: Wieland
authors: I
authors: I
authors: Heinrichs
authors: J F
authors: JF
authors: Prior
authors: T H
authors: TH
authors: Huisman
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D003062:Codon; D005914:Globins / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; C065670:hemoglobin Dhonburi; D005914:Globins