IthaID: 1008
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 63 CAT>AAT [His>Asn] | HGVS Name: | HBB:c.190C>A |
| Hb Name: | Hb Haná | Protein Info: | β 63(E7) His>Asn |
Context nucleotide sequence:
TATGGGCAACCCTAAGGTGAAGGCT [C>A] ATGGCAAGAAAGTGCTCGGTGCCTT (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKANGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: The mutation replaces a hydrophobic amino acid (His) for a hydrophilic amino acid (Asn), likely affecting the hydrophobic properties of the heme microenvironment. Initially reported in a heterozygous state in a Czech proband and her sister with Heinz body hemolytic anemia and elevated levels of methaemoglobin. The mother with the same mutation, who is also a smoker, is asymptomatic and had no anemia nor signs of hemolysis. Also found in a heterozygous state in a Senegalese proband and her mother, both presenting with chronic asthenia associated with intermittent headaches, moderate anemia and elevated levels of methaemoglobin. Due to the proband's dark skin, cyanosis was not clinically detectable.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-chain variant |
| Allele Phenotype: | Methemoglobinaemia |
| Stability: | Unstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 70914 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 2 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | N/A |
| Ethnic Origin: | Czech, Senegalese |
| Molecular mechanism: | Altered heme pocket |
| Inheritance: | Dominant |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Divoký V, Luhový M, Divoká M, Melichárková R, Pospísilová , Indrák K, [Hemoglobin Haná or alpha 2 beta 2 63 (E7) His-Asn: a new unstable hemoglobin variant with a paradoxically different clinical manifestations in smokers and non-smokers in the same family], Vnitr̆ní lékar̆ství, 43(5), 267-72, 1997
- Mojzikova R, Dolezel P, Pavlicek J, Mlejnek P, Pospisilova D, Divoky V, Partial glutathione reductase deficiency as a cause of diverse clinical manifestations in a family with unstable hemoglobin (Hemoglobin Haná, β63(E7) His-Asn)., Blood Cells Mol Dis, 45(3), 219-22, 2010
- Le Calvez B, Delecourt-Billet M, Grain A, Couque N, Leblanc T, Congenital methaemoglobinaemia and chronic haemolysis related to a rare form of unstable haemoglobin: Efficacy of riboflavin on clinical and biological features., Br J Haematol, 2022