title: Two novel α2 gene mutations causing altered amino acid sequences produce a mild (Hb Kinshasa, HBA2: c.428A > T) and severe (HBA2: c.342-345insCC) α-thalassemia phenotype.
abstract: We describe two novel α2 gene mutations that result in an altered amino acid sequence. In case 1, the α2 stop codon was mutated from TAA > TTA (HBA2: c.428A > T), resulting in an α2 protein chain extension of 31 amino acids. The new hemoglobin (Hb) variant was named Hb Kinshasa for the place of origin of the patient. This patient was also a carrier of Hb S (HBB: c.20A > T), which was expressed at reduced levels, but had an otherwise normal blood count. For cases 2 and 3, an α2 frameshift mutation caused a premature α2 protein chain termination at position 133 (HBA2: c.342-345insCC). The phenotype of this mutation seems to be rather severe as judged by the pronounced microcytosis and hypochromia observed in case 2. In addition, the father of this patient (case 3) also carried a β(0)-thalassemia (β(0)-thal) mutation (HBB: c.118C > T).
authors: Institute for Medical & Molecular Diagnostics Ltd. , Zürich , Switzerland.
authors: Elisabeth
authors: E
authors: Saller
authors: Fabrizio
authors: F
authors: Dutly
authors: Hannes
authors: H
authors: Frischknecht
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D000755:Anemia, Sickle Cell / Q000175:diagnosis / Q000235:genetics; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004909:Erythrocyte Indices; D005260:Female; D005838:Genotype; D006443:Hemoglobin A2 / Q000235:genetics*; D006451:Hemoglobin, Sickle / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D006451:Hemoglobin, Sickle; D055542:alpha-Globins; D006443:Hemoglobin A2
keywords: exon 3 frameshift; termination codon mutation; α2-Globin chain