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: G D Efremov, L Simjanovska, D Plaseska-Karanfilska, E Stanojevic, G H Petkov
• Journal: Acta haematologica (Acta Haematol) Vol. 117 Issue 1 Pg. 1-7 ( 2007) ISSN: 0001-5792 [Print] Switzerland
• PMID: 17095853 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2007 S. Karger AG, Basel

Chemical References

• Hemoglobins, Abnormal
• RNA, Messenger
• hemoglobin Jambol
• Globins

Topics

• Amino Acid Sequence
• Anemia, Hemolytic, Congenital (genetics)
• Base Sequence
• Bulgaria
• Chromosome Inversion
• DNA Mutational Analysis
• Female
• Globins (genetics)
• Hemoglobins, Abnormal (chemistry, genetics, isolation & purification)
• Humans
• Infant
• Molecular Sequence Data
• Mutagenesis, Insertional
• Phenotype
• Polymerase Chain Reaction
• Protein Denaturation
• RNA, Messenger (genetics)
• Sequence Deletion