IthaID: 1021
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 67 GTG>ATG [Val>Met] | HGVS Name: | HBB:c.202G>A |
| Hb Name: | Hb Alesha | Protein Info: | β 67(E11) Val>Met |
Context nucleotide sequence:
TAAGGTGAAGGCTCATGGCAAGAAA [A/G] TGCTCGGTGCCTTTAGTGATGGCCT (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKMLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as: Hb Bristol-Alesha, Hb Bristol
Comments: Valine changes to a methionine residue at position β67(E11). This Hb variant is the same as Hb Bristol, initially characterized by protein analysis as a β67(E11)Val>Asp substitution. The Met molecule is first generated at 67[E11] and then posttranslationally converted to the Asp molecule. The Met>Asp conversion is directly related to accelerated autoxidation, H2O2 being the causative agent. The results of Hb electrophoresis, IEF, HPLC and reversed phase HPLC vary, and in some cases the anomalous Hb cannot be detected by these methods. Hb Bristol and Hb Alesha are considered the same, and the condition is now termed Hb Bristol-Alesha. Overall, the introduction of the larger methionine residue into the heme pocket and the loss of the bonds between valine at β67 and the heme group, produce an unstable Hb and severe hemolysis.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-chain variant |
| Allele Phenotype: | Thalassaemia dominant |
| Stability: | Unstable |
| Oxygen Affinity: | Decreased Oxygen Affinity |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 70926 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 2 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Russian, mixed Indian European, Japanese, English, Argentinian, German |
| Molecular mechanism: | Altered heme pocket |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Molchanova TP, Postnikov YuV , Pobedimskaya DD, Smetanina NS, Moschan AA, Kazanetz EG, Tokarev YuN , Huisman TH, Hb Alesha or alpha 2 beta (2)67(E11)Val-->Met: a new unstable hemoglobin variant identified through sequencing of amplified DNA., Hemoglobin, 17(3), 217-25, 1993
- Rees DC, Rochette J, Schofield C, Green B, Morris M, Parker NE, Sasaki H, Tanaka A, Ohba Y, Clegg JB, A novel silent posttranslational mechanism converts methionine to aspartate in hemoglobin Bristol (beta 67[E11] Val-Met->Asp)., Blood, 88(1), 341-8, 1996
- Kano G, Morimoto A, Hibi S, Tokuda C, Todo S, Sugimoto T, Harano T, Miyazaki A, Shimizu A, Imashuku S, Hb Bristol-Alesha presenting thalassemia-type hyperunstable hemoglobinopathy., International journal of hematology, 80(5), 410-5, 2004
- Eberle SE, Noguera NI, Sciuccati G, Bonduel M, Díaz L, Staciuk R, Targovnik HM, Feliu-Torres A, Hb Alesha [beta67(E11)Val-->Met, GTG-->ATG] in an Argentinean girl., Hemoglobin, 31(3), 379-82, 2007
- Pedroso GA, Kimura EM, Santos MNN, Albuquerque DM, Ferruzzi JLH, Jorge SE, Costa FF, Saad STO, Sonati MF, Coinheritance of Hb Bristol-Alesha [β67(E11)Val→Met; HBB: c.202G>A] and the α212 Patchwork Allele in a Brazilian Child with Severe Congenital Hemolytic Anemia., Hemoglobin , 41(3), 203-208, 2017
- Hamid M, Zargan Nezhad E, Galehdari H, Saberi A, Shariati G, Sedaghat A, A First Report of Hb Alesha [β67(E11)Val>Met, GTG>ATG] in an Iranian Patient., Iran Biomed J, 23(6), 429-31, 2019
- Zhang Q, Shi HC, Liu N, [Hb Alesha of unstable hemoglobinopathy: a case report and literature review]., Zhonghua Xue Ye Xue Za Zhi, 42(2), 158-160, 2021