title: Hb Jambol: a new hyperunstable hemoglobin causing severe hemolytic anemia.
abstract: We describe a new hyperunstable beta-chain variant due to a complex genomic rearrangement. The abnormal hemoglobin (Hb) was found as a de novo mutation in a 2-year-old Bulgarian girl with severe hemolytic anemia. The mutation was detected through RNA/DNA analysis. It represents a complex genomic rearrangement involving an insertion of 23 nts after IVS-II-535 (derived by triplication of the 12-nts adjacent sequence and subsequent deletion of 1 nt), a deletion of 310 nts extending from IVS-II-550 to the first nt of Cd 108 and an insertion of 28 nts at the deletion junctions (derived from the inverted sequence between nts +3,707 and +3,734 3' to the beta-globin gene termination codon). At the protein level this mutation leads to a deletion of 4 amino acid residues (Leu-Leu-Glu-Asn) at positions 105-108 and an insertion of 9 residues (Val-Pro-Ser-Val-Thr-Leu-Phe-Phe-Asp) at the same location, creating an abnormal elongated beta-chain of 151 amino acid residues. This highly unstable variant was named 'Hb Jambol' after the geographic location in which the patient resides.
authors.affiliation: Research Center for Genetic Engineering and Biotechnology, Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia. gde@manu.edu.mk
authors.forename: G D
authors.initials: GD
authors.lastname: Efremov
authors.forename: L
authors.initials: L
authors.lastname: Simjanovska
authors.forename: D
authors.initials: D
authors.lastname: Plaseska-Karanfilska
authors.forename: E
authors.initials: E
authors.lastname: Stanojevic
authors.forename: G H
authors.initials: GH
authors.lastname: Petkov
mesh_terms: D000595:Amino Acid Sequence; D000745:Anemia, Hemolytic, Congenital / Q000235:genetics*; D001483:Base Sequence; D002031:Bulgaria; D007446:Chromosome Inversion; D004252:DNA Mutational Analysis; D005260:Female; D005914:Globins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011489:Protein Denaturation; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D006455:Hemoglobins, Abnormal; D012333:RNA, Messenger; C517126:hemoglobin Jambol; D005914:Globins