IthaID: 406

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.

Heterozygous records (preview in IthaPhen)

1. 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 PubMed
2. 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 PubMed
3. 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 PubMed
4. 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 PubMed
5. Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013 PubMed
6. 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 PubMed