IthaID: 1166
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 106 CTG>CCG [Leu>Pro] | HGVS Name: | HBB:c.320T>C |
| Hb Name: | Hb Southampton | Protein Info: | β 106(G8) Leu>Pro |
Context nucleotide sequence:
CCTCTTATCTTCCTCCCACAGCTCC [A/C/G/T] GGGCAACGTGCTGGTCTGTGTGCTG (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLPGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as: Hb Casper
Comments: Rare haemoglobin (Hb) variant reported as a de novo mutation in a handful of patients from various ethnic backgrounds. The β106 Leu>Pro substitution disrupts the alpha helix of the β-chain and alters the tertiary structure of the Hb molecule at a point where there is direct contact with heme, resulting in the loss of the heme group. The variant can be detected by isoelectric focusing (IEF) but it is electrophoretically silent in conventional Hb electrophoresis. Detection of inclusion bodies and highly unstable Hb.
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: | Hyperunstable |
| Oxygen Affinity: | Increased Oxygen Affinity |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 71894 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 3 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | N/A |
| Ethnic Origin: | Argentinean | Caucasian | English | Uruguayan | Chinese | Hispanic |
| Molecular mechanism: | Altered heme pocket |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Hyde RD, Hall MD, Wiltshire BG, Lehmann H, Haemoglobin Southampton, 106 (G8) Leu leads to pro: an unstable variant producing severe haemolysis., Lancet, 2(7788), 1170-2, 1972
- Koler RD, Jones RT, Bigley RH, Litt M, Lovrien E, Brooks R, Lahey ME, Fowler R, Hemoglobin Casper: beta 106 (G8) Leu leads to Pro; a contemporary mutation., The American journal of medicine, 55(3), 549-58, 1973
- Wajcman H, Gacon G, Labie D, Koler RD, Jones RT, Isolation and functional characterization of hemoglobin Casper: beta106(G8) Leu replaced by Pro., Biochemistry, 14(22), 5017-20, 1975
- Didkovskiĭ NA, Idel'son LI, Filippova AV, Lemann G, [A new case of the unstable hemoglobin Southampton--Casper(beta106) (G68) leucine--proline)]., Probl Gematol Pereliv Krovi, 21(6), 48-50, 1976
- Heintz NH, Howard PL, Hemoglobin Southampton (Casper): characterization of the base mutation., Am. J. Hematol., 30(1), 1-3, 1989
- Eandi Eberle S, Noguera NI, Sciuccati G, Bonduel M, Díaz L, Staciuk R, Feliu-Torres A, Hb Southampton [beta106(G8)Leu-->Pro, CTG-->CCG] in an Argentinean boy., Hemoglobin, 30(3), 401-3, 2006
- Avalos Gómez V, Eandi Eberle S, Pepe C, Sciuccati G, García Rosolen N, Cervio C, Díaz L, Candás A, Bonduel M, Piazza G, Chaves D, Feliú Torres A, [Severe hemolytic anemia due to hemoglobin Southampton: case report]., Arch Argent Pediatr, 110(5), e91-4, 2012
- Pereira JA, López P, Costa FF, Sans M, Sonati Mde F, Hb Southampton [B106(G8)Leu→PRO, CTG→CCG] in a Uruguayan woman., Rev Bras Hematol Hemoter, 35(2), 146-7, 2013
- Haque A, Quint DJ, Castle VP, Leber SM, Another Rare Unstable Hemoglobinopathy: Hemoglobin Casper/Southampton Associated with Moyamoya Disease., Cerebrovasc Dis Extra, 5(2), 52-4, 2015
- Liu J, Huang Y, Lei Y, Lai Y, Hb Southampton [β106(G8)Leu→Pro; HBB: c.320T>C] and Codons 41/42 (-TTCT; HBB: c.124_127delTTCT) in a Chinese Girl., Hemoglobin, 41(2), 134-136, 2017