IthaID: 379
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 59 GGC>CGC [Gly>Arg] | HGVS Name: | HBA2:c.178G>C |
| Hb Name: | Hb Zurich-Albisrieden | Protein Info: | α2 59(E8) Gly>Arg |
Context nucleotide sequence:
CGGCTCTGCCCAGGTTAAGGGCCAC [G>C] GCAAGAAGGTGGCCGACGCGCTGAC (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHRKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR
Also known as:
Comments: Rare and highly unstable variant. Reported in a heterozygote with persistent hypochromic microcytosis and erythrocytosis. Not detectable in blood; no abnormal Hb fraction by ion exchange and reversed phase chromatography, IEF, ESIMS [PMID: 15658192]. Reported with the – –SEA a0-thal deletion [IthaID: 309] in a fetus with Hb Bart’s hydrops fetalis. The father was heterozygous with α-thal trait [PMID: 27686733]. Reported as a homozygote with severe congenital hemolytic anemia and ineffective erythropoiesis (consanguineous family) [PMID: 30151892]. Reported with α+ Hb Sallanches [IthaID: 396] in a male with persistent microcytosis, hypochromia, and reticulocytosis. Positive instability tests [PMID: 31930682].
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⁺ |
| Stability: | Hyperunstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 34070 |
| Size: | 1 bp |
| Located at: | α2 |
| Specific Location: | Exon 2 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Swiss, Chinese, Brazilian, Indian |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Dutly F, Fehr J, Goede JS, Morf M, Troxler H, Frischknecht H, A new highly unstable alpha chain variant causing alpha(+)-thalassemia: Hb Zurich Albisrieden [alpha59(E8)Gly-->Arg (alpha2)]., Hemoglobin, 28(4), 347-51, 2004
- Yang Xin,Yan Jin-Mei,Li Jian,Xie Xing-Mei,Zhou Jian-Ying,Li Yan,Li Dong-Zhi, Hydrops Fetalis Associated with Compound Heterozygosity for Hb Zurich-Albisrieden (HBA2: C.178G > C) and the Southeast Asian (- -SEA/) Deletion., Hemoglobin, 5(5), 353-355, 2017
- Pedroso GA, Kimura EM, Santos MNN, Albuquerque DM, Malimpensa D, Jorge SE, Verissimo MPA, Costa FF, Sonati MF, Thalassemia major phenotype caused by HB Zürich-Albisrieden [α2 59(E8) Gly > Arg (HBA2:C.178G > C)] in a Brazilian child., Pediatr Blood Cancer, 65(12), e27413, 2018
- Sharma P, Das R, Khadwal AR, Karmakar I, Hira JK, Chhabra S, HbH disease due to compound heterozygosity for hemoglobins Zürich-Albisrieden and Sallanches., Pediatr Blood Cancer, 67(4), e28161, 2020