IthaID: 2285

Context nucleotide sequence:
GCCGCCTGGGGTAAGGTCGGCGCGC [A>C] CGCTGGCGAGTATGGTGCGGAGGCC (Strand: +)

Protein sequence:
MVLSPADKTNVKAAWGKVGAPAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR

Also known as: Hb Anderlecht

Comments: Initially identified by protein analysis as a His>Pro change at position α20 (α1 or α2) in a Congolese newborn and his mother and was reported as a hematologically and clinically silent variant. It was later detected by sequencing in an African-American as an α1 gene change. The α20 residue is found in the B helix, external in the Hb structure where any change in hydrophobicity leads to a large effect on the mobility. This variant is detectable by various electrophoretic methods (IEF, CAE alkaline, Citrate agar, HPLC). Molecular modelling showed that α20 His>Pro substitution did not disrupt helical structure or impact interchain interactions. The histine at α20 is likely involved in the axial intermolecular contacts of the deoxyHb S fibers, making a polar bridge with glutamic acid at β20. It is speculated that the His>Pro change could modify the rate of polymerization of deoxyHb S and the clinical severity of SCD. However, the coinheritance of this variant with heterozygous -α3.7 and Hb SC disease in the African-American proband was associated with a mild phenotype, consisting of microcytosis and anisocytosis, but no anemia or other hematological abnormality.

We follow the HGVS sequence variant nomenclature and IUPAC standards.

Heterozygous records (preview in IthaPhen)

1. Cotton F, Wajcman H, Hansen V, Lin C, Jotzo K, Haumont D, Promé D, Riou J, Miyazaki A, Galactéros F, Vertongen F, Gulbis B, Hb Anderlecht [alpha20(B1)His-->Pro]: a silent variant found in a Congolese newborn., Hemoglobin , 24(4), 299-304, 2000 PubMed
2. Zhuang L, Patel N, Bryant S, Kutlar A, Kutlar F, Young AN, Hb Fulton-Georgia [α20(B1)His→Pro; HBA1: c.62A>C]: A New α-Globin Variant Coinherited with α-Thalassemia-2 (3.7 kb deletion) and Hb SC Disease., Hemoglobin , 37(5), 481-5, 2013 PubMed