IthaID: 995
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 58 CCT>CGT [Pro>Arg] | HGVS Name: | HBB:c.176C>G |
| Hb Name: | Hb Dhofar | Protein Info: | β 58(E2) Pro>Arg |
Context nucleotide sequence:
ACTCCTGATGCTGTTATGGGCAACC [C>G] TAAGGTGAAGGCTCATGGCAAGAAA (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNRKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: Heterozygotes presented with lower levels of Hb Dhofar (~15%) than expected. Hb Dhofar found in cis with CD 29 GGC>GGT, first in a young man [PMID: 7786794] and then in 54 cases in a cohort study [PMID: 18173741], explaining the lower levels of Dhofar. The CD 29 (C>T) occurs in the consensus splice site boundary of β-globin exon 1, and although it does not alter the amino acid it interferes with the normal mRNA splicing process. All heterozygotes cases presented with elevated Hb A2 and decreased MCV and MCH, consistent with β-thalassaemia trait.
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: | 70900 |
| 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: | Qara tribesmen in Southern Arabia |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
HPLC
| ID | Hb Variant | Gene | Instrument | Method | Area (%) | Ret Time (min) | Comments | ||
|---|---|---|---|---|---|---|---|---|---|
| 65 | Hb Dhofar | β | D-10 | Dual Kit Program | 23.5 | 3.43 | Thalassemic Hb (in cis with a beta (+)-thalassemic mutation). | [PDF] | |
| 67 | Hb Dhofar | β | VARIANT | β-thal Short Program | 13.9 | 3.84 | Thalassemic Hb (in cis with a beta (+)-thalassemic mutation). | [PDF] | |
| 68 | Hb Dhofar | β | VARIANT II | β-thal Short Program | 12.8 | 3.92 | Thalassemic Hb (in cis with a beta (+)-thalassemic mutation). | [PDF] | |
| 69 | Hb Dhofar | β | VARIANT II | Dual Kit Program | 18.9 | 3.12 | Thalassemic Hb (in cis with a beta (+)-thalassemic mutation). | [PDF] |
In silico pathogenicity prediction
Frequencies
Publications / Origin
- Marengo-Rowe AJ, Lorkin PA, Gallo E, Lehmann H, Haemoglobin Dhofar--a new variant from Southern Arabia., Biochimica et biophysica acta, 168(1), 58-63, 1968
- Williamson D, Brown KP, Langdown JV, Baglin TP, Haemoglobin Dhofar is linked to the codon 29 C-->T (IVS-1 nt-3) splice mutation which causes beta+ thalassaemia., Br J Haematol, 90(1), 229-31, 1995
- Daar S, Gravell D, Hussein HM, Pathare AV, Wali Y, Krishnamoorthy R, Haematological and clinical features of beta-thalassaemia associated with Hb Dhofar., Eur J Haematol, 80(1), 67-70, 2008