title: Beta-thalassemia due to a novel nonsense mutation at codon 37 (TGG-->TAG) found in an Afghanistani family.
abstract: We have identified and characterized a novel beta-thalassemic mutation in an Afghanistanifamily. The molecular pathology consists of a single base substitution (TGG-->TAG) at codon 37 of the beta-globin gene, giving rise to a stop codon (TAG). Premature stop of translation results in a truncated protein and usually the phenotype of beta-thalassemia (thal) major in homozygous individuals. However, this was not the case in our proband, who was homozygous for the codon 37 mutation. He presented with the phenotype of thalassemia intermedia with a hemoglobin (Hb) level of 8.1 g/dL and no previous history of blood transfusions. High performance liquid chromatography (HPLC) analysis showed exclusively Hb F except for a Hb A2 level within normal limits. Subsequent analysis demonstrated homozygosity for the XmnI Ggamma polymorphism and heterozygosity for a deletional alpha-thal (alphaalpha/-alpha(-3.7)). These findings might, at least partly, explain the beta-thal intermedia phenotype observed in the proband.
authors.affiliation: Department of Haematology, Herlev University Hospital, Center for Haemoglobin Disorders, Herlev, Denmark.
authors.forename: Brian
authors.initials: B
authors.lastname: Kornblit
authors.forename: Pia
authors.initials: P
authors.lastname: Taaning
authors.forename: Henrik
authors.initials: H
authors.lastname: Birgens
mesh_terms: D000328:Adult; D000346:Afghanistan; D002648:Child; D003062:Codon / Q000097:blood / Q000235:genetics*; D018389:Codon, Nonsense; D005190:Family; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis; D005914:Globins / Q000032:analysis / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000032:analysis; D006801:Humans; D008297:Male; D010641:Phenotype; D017354:Point Mutation; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D003062:Codon; D018389:Codon, Nonsense; D006455:Hemoglobins, Abnormal; D005914:Globins; D005319:Fetal Hemoglobin