HB Hillingdon [α46(CE4)Phe→Val (α1 Or α2)]: A New α Chain Hemoglobin Variant

Abstract

Routine antenatal hemoglobinopathy screening detected a new alpha chain variant that eluted with Hb A(2) on cation exchange high performance liquid chromatography (HPLC) in a lady of Sri Lankan origin who had normal hematological indices. The mutation was identified by electrospray ionization mass spectrometry (ESI-MS) as alpha46(CE4)Phe-->Val, inferring that the variant was due to a single base change at codon 46 (TTC>GTC) of the alpha1- or alpha2-globin genes.

In SilicoAnalysis of the Effects of Point Mutations on α-Globin: Implications for α-Thalassemia

“…These models generally predicted only minor changes to α-helical regions of the proteins, and no changes to other regions. Three variants were predicted to have changes in protein structure resulting in the loss of the heme cofactor -α46Phe>Val (Hb Hillingdon; initially wrongly predicted to be asymptomatic), α65Ala>Thr (Hb Part-Dieu; clinical reports of hepatosplenomegaly, albeit confused by the patient's diabetes) and α136Leu>Met (Hb Chicago) [26][27][28]. In other variants (e.g.Hb Westmead; α122His>Gln) the amino acid substitutions occur at an α1β1 contact site within the hemoglobin tetramer, but are predicted to be neutral by PredictSNP [29].…”

Hb Lake Tapawingo [α46(CE4)Phe→Ser; HBA2:c.140T>C]: A New Unstable α Chain Hemoglobin Variant Associated with Low Systemic Arterial Saturation

“…Hb Rockaway is a stable variant that co-elutes with Hb A on CE-HPLC and causes no clinical effects (2). Hb Hillingdon is also clinically asymptomatic and is similar to Hb Lake Tapawingo in that it co-elutues with Hb A 2 on CE-HPLC (3). The Phe→Ser of Hb Lake Tapawingo substitutes an uncharged polar side chain for a nonpolar residue.…”