IthaID: 1089
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 87 ACA>ATA | HGVS Name: | HBB:c.263C>T |
| Hb Name: | Hb Quebec-Chori | Protein Info: | β 87(F3) Thr>Ile |
Context nucleotide sequence:
GACAACCTCAAGGGCACCTTTGCCA [C/T] ACTGAGTGAGCTGCACTGTGACAAG (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFAILSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: Hb Quebec-Chori is mainly found in individuals diagnosed with sickle cell trait, but with multiple complications consistent with sickle cell disease. It is an electrophoretically silent Hb variant with normal oxygen tension (P50). The β Quebec-Chori globin chain can be detected on reversed-phase chromatography, Triton-urea gel electrophoresis and ESI MS. The genetic variant is located at the site of the β-globin chain involved in lateral contacts between sickle fibers. The hydrophobic βVal6 residue interacts with the hydrophobic pocket formed by βPhe85 and βLeu88 on a neighboring Hb tetramer, favoring deoxy-HbS polymerization. It is speculated that the β87 Thr>Ile change (Ile=hydrophobic residue) at the lateral contact site supports the formation of the HbS polymer.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-chain variant |
| Allele Phenotype: | N/A |
| Stability: | N/A |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 70987 |
| 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: | Canadian | English | French | Ghanaian | Irish |
| Molecular mechanism: | Altered interaction with HbS polymer |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Witkowska HE, Lubin BH, Beuzard Y, Baruchel S, Esseltine DW, Vichinsky EP, Kleman KM, Bardakdjian-Michau J, Pinkoski L, Cahn S, Sickle cell disease in a patient with sickle cell trait and compound heterozygosity for hemoglobin S and hemoglobin Quebec-Chori., The New England journal of medicine, 325(16), 1150-4, 1991
- Segal L, Discepola M, Idiopathic intracranial hypertension and sickle cell disease: two case reports., Can J Ophthalmol, 40(6), 764-7, 2005
- Tubman VN, Bennett CM, Luo HY, Chui DH, Heeney MM, Sickle cell disease caused by Hb S/Québec-CHORI: treatment with hydroxyurea and response., Pediatr Blood Cancer, 49(2), 207-10, 2007
- Goode E, Boruchov D, Oliveira JL, Lau CC, Hemoglobin S/Hemoglobin Quebec-Chori Presenting as Sickle Cell Disease: A Case Report., J Pediatr Hematol Oncol, 42(8), e775-e777, 2020