IthaID: 2285
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 20 CAC>CCC [His>Pro] | HGVS Name: | HBA1:c.62A>C |
| Hb Name: | Hb Fulton-Georgia | Protein Info: | α1 20(B1) His>Pro |
Context nucleotide sequence:
GCCGCCTGGGGTAAGGTCGGCGCGC [A>C] CGCTGGCGAGTATGGTGCGGAGGCC (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAPAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR
Also known as: Hb Anderlecht
Comments: Initially identified by protein analysis as a His>Pro change at position α20 (α1 or α2) in a Congolese newborn and his mother and was reported as a hematologically and clinically silent variant. It was later detected by sequencing in an African-American as an α1 gene change. The α20 residue is found in the B helix, external in the Hb structure where any change in hydrophobicity leads to a large effect on the mobility. This variant is detectable by various electrophoretic methods (IEF, CAE alkaline, Citrate agar, HPLC). Molecular modelling showed that α20 His>Pro substitution did not disrupt helical structure or impact interchain interactions. The histine at α20 is likely involved in the axial intermolecular contacts of the deoxyHb S fibers, making a polar bridge with glutamic acid at β20. It is speculated that the His>Pro change could modify the rate of polymerization of deoxyHb S and the clinical severity of SCD. However, the coinheritance of this variant with heterozygous -α3.7 and Hb SC disease in the African-American proband was associated with a mild phenotype, consisting of microcytosis and anisocytosis, but no anemia or other hematological abnormality.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | α-chain variant |
| Allele Phenotype: | N/A |
| Stability: | N/A |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 37641 |
| Size: | 1 bp |
| Located at: | α1 |
| Specific Location: | Exon 1 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | African-American, Congolese |
| Molecular mechanism: | Altered secondary structure |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Cotton F, Wajcman H, Hansen V, Lin C, Jotzo K, Haumont D, Promé D, Riou J, Miyazaki A, Galactéros F, Vertongen F, Gulbis B, Hb Anderlecht [alpha20(B1)His-->Pro]: a silent variant found in a Congolese newborn., Hemoglobin , 24(4), 299-304, 2000
- Zhuang L, Patel N, Bryant S, Kutlar A, Kutlar F, Young AN, Hb Fulton-Georgia [α20(B1)His→Pro; HBA1: c.62A>C]: A New α-Globin Variant Coinherited with α-Thalassemia-2 (3.7 kb deletion) and Hb SC Disease., Hemoglobin , 37(5), 481-5, 2013