title: Combination of Hb Knossos [Cod 27 (G-T)] and IVSII-745 (C-G) in a Turkish patient with beta-thalassemia major.
abstract: Beta-thalassemia is the most common disease among hemoglobinopathies in Antalya, Turkey, as well as world-wide. Mutations found in Turkish beta-thalassemia patients constitute a heterogeneous group, consisting mostly of point mutations. Only in very rare cases did deletions or insertions cause affected or carrier phenotypes. Hb Knossos [beta 27 (B9) Ala-Ser] is a rare variant with a normal HbA2 level. In this study, we aimed to investigate the effect of compound heterozygosity for Hb Knossos [Cod 27 (G-T)] and IVSII-745 (C-G). To our knowledge, this is the first report of such a combination related with beta-thalassemia major phenotype in a Turkish family, where reverse dot blot hybridization (RDBH) and DNA sequencing analysis were used. Heterozygous inheritance of the mutation results in mild beta-thalassemia phenotype, whereas homozygous inheritance leads to intermediate beta-thalassemia. As a result, the compound heterozygosity of Hb Knossos with IVSII-745 appears as the cause of the beta-thalassemia major phenotype in our case. The combination of these mutations [Hb Knossos, Cod 27 (G-T), and IVSII-745, C-G] causes the beta-thalassemia major phenotype, and this is important for genetic counseling.
authors.affiliation: Department of Medical Biology and Genetics, Medical School, Akdeniz University, 07070, Antalya, Turkey. keser@akdeniz.edu.tr
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Keser
authors.forename: Esra
authors.initials: E
authors.lastname: Manguoglu
authors.forename: Ozlem
authors.initials: O
authors.lastname: Kayisli
authors.forename: Akif
authors.initials: A
authors.lastname: Yesilipek
authors.forename: Guven
authors.initials: G
authors.lastname: Luleci
mesh_terms: D001483:Base Sequence; D002648:Child; D003062:Codon; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA; D014421:Turkey; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; C036232:hemoglobin Knossos