title: A novel beta-Thalassemic allele due to a two nucleotide deletion: beta76 (-GC).
abstract: We have identified and characterized a novel beta-thalassemic mutation in a North African adult. The molecular defect consists of a two nucleotide (nt) deletion in the beta-globin gene at codon 76 [beta76 (-GC), c.229-230delGC]. This frameshift mutation generates a TGA stop codon at position 89. The carrier presented with mild microcytic anemia (Hb 12.8 g/dL, MCV 60 fL), no detectable Hb F, an elevated Hb A2 level (5.5%) with no other mutation in the beta-globin gene and none of the more common known deletions in the alpha-globin cluster. No abnormal hemoglobin (Hb) was present in routine electrophoresis or in high performance liquid chromatography (HPLC) analyses. Pathologic inclusions were absent in both mature red cells and in reticulocytes. This observation reinforces the hypothesis that nonsense and frameshift mutations that result in a premature stop codon in exon 1 or exon 2 inherited in the heterozygous state do not generate dominant beta-thalassemia (thal). This is the first example of a premature stop codon at position 89.
authors: Service de Génétique Moléculaire Médicale & UPRES EA 3901, Centre Hospitalier Universitaire, Amiens, France.
authors: Karine
authors: K
authors: Foulon
authors: Jacques
authors: J
authors: Rochette
authors: Estelle
authors: E
authors: Cadet
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000747:Anemia, Hypochromic / Q000235:genetics*; D001483:Base Sequence; D018388:Codon, Terminator / Q000502:physiology; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation / Q000502:physiology; D017353:Gene Deletion; D005914:Globins / Q000235:genetics*; D006443:Hemoglobin A2 / Q000032:analysis; D006801:Humans; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D018388:Codon, Terminator; D005914:Globins; D006443:Hemoglobin A2