IthaID: 406
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 119 CCT>TCT [Pro>Ser] | HGVS Name: | HBA1:c.358C>T |
| Hb Name: | Hb Groene Hart | Protein Info: | α1 119(H2) Pro>Ser |
Context nucleotide sequence:
CGCCCACCTCCCCGCCGAGTTCACC [C/T] CTGCGGTGCACGCCTCCCTGGACAA (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTSAVHASLDKFLASVSTVLTSKYR
Also known as: Hb Bemalda P, Hb Bernalda
Comments: Proline in position α117 (H2) is an α helix initiator, involved in the secondary conformation of the α-globin chain. Pro>Ser replacement disturbs the α1β1 contact, which increases the concentration of unstable free globin chains. The mutation also impairs interaction with the α-haemoglobin stabilizing protein (AHSP), which leads to α chain pool reduction and α-thalassaemia phenotype ([PMID: 17052927] for in vitro assay). First reported in heterozygotes of a Moroccan family with a mild α-thalassaemia phenotype. Reported in a number of heterozygotes, homozygotes and compound heterozygotes with the -α3.7 deletion from Morocco, Algeria and Tunisia. Unstable variant characterized by DNA sequencing (several methods failed to detect an abnormal native or denatured haemoglobin). Microcytic hypochromic parameters reported in all cases.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Thalassaemia and Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | α-thalassaemia, α-chain variant |
| Allele Phenotype: | α⁺ Thalassaemia |
| Stability: | Unstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 38203 |
| Size: | 1 bp |
| Located at: | α1 |
| Specific Location: | Exon 3 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Moroccan, Algerian, Tunisian |
| Molecular mechanism: | Altered α1β1 interface |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
HPLC
| ID | Hb Variant | Gene | Instrument | Method | Area (%) | Ret Time (min) | Comments | ||
|---|---|---|---|---|---|---|---|---|---|
| 207 | Hb Groene Hart | α1 | D-10 | Dual Kit Program | 79.6 | 1.68 | Mild non-deletional alpha thal variant. Migrates as HbA. | [PDF] | |
| 208 | Hb Groene Hart | α1 | VARIANT | β-thal Short Program | 81.9 | 2.46 | Mild non-deletional alpha thal variant. Migrates as HbA. | [PDF] | |
| 209 | Hb Groene Hart | α1 | VARIANT II | β-thal Short Program | 82.4 | 2.5 | Mild non-deletional alpha thal variant. Migrates as HbA. | [PDF] | |
| 210 | Hb Groene Hart | α1 | VARIANT II | Dual Kit Program | 80 | 1.772 | Mild non-deletional alpha thal variant. Migrates as HbA. | [PDF] |
In silico pathogenicity prediction
Frequencies
Publications / Origin
- Harteveld CL, van Delft P, Plug R, Versteegh FG, Hagen B, van Rooijen I, Kok PJ, Wajcman H, Kister J, Giordano PC, Hb Groene Hart: a new Pro-->Ser amino acid substitution at position 119 of the alpha1-globin chain is associated with a mild alpha-thalassemia phenotype., Hemoglobin, 26(3), 255-60, 2002
- Siala H, Ouali F, Messaoud T, Sfar R, Fattoum S, First description in Tunisia of a point mutation at codon 119 (CCT-->TCT) in the alpha1-globin gene: Hb Groene Hart in association with the -alpha3.7 deletion., Hemoglobin, 29(4), 263-8, 2005
- Vasseur-Godbillon C, Marden MC, Giordano P, Wajcman H, Baudin-Creuza V, Impaired binding of AHSP to alpha chain variants: Hb Groene Hart illustrates a mechanism leading to unstable hemoglobins with alpha thalassemic like syndrome., Blood Cells Mol. Dis., 37(3), 173-9, 2006
- Giordano PC, Zweegman S, Akkermans N, Arkesteijn SG, van Delft P, Versteegh FG, Wajcman H, Harteveld CL, The first case of Hb Groene Hart [alpha119(H2)Pro-->Ser, CCT-->TCT (alpha1)] homozygosity confirms that a thalassemia phenotype is associated with this abnormal hemoglobin variant., Hemoglobin, 31(2), 179-82, 2007
- Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013
- Joly P, Lacan P, Garcia C, Francina A, Description of the phenotypes of 63 heterozygous, homozygous and compound heterozygous patients carrying the Hb Groene Hart [α119(H2)Pro→Ser; HBA1: c.358C>T] variant., Hemoglobin, 38(1), 64-6, 2014