Hb HARLEQUIN [b76(E20)Ala->Val]: A NEUTRAL VARIANT FOUND DURING DIABETIC MONITORING
Wajcman H1,*, Riou J1, Henthorn J2, Promé D3, Richelme-David S3, Galactéros F1
*Corresponding Author: DrDr. Henri Wajcman, INSERM U468, Génétique Moléculaire et Physiopathologie, Hôpital Henri Mondor, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Créteil Cédex, France; Tel: +33 149813578; Fax: +33 148993345; E-mail: wajcman@im3.inserm.fr
page: 7

DISCUSSION

Two other variants affecting the β76(E20) position have been described. This site is directed towards the exterior of the molecule and is near to the entry of the central cavity located between the two β chains (Fig. 4). The first variant is Hb J-Chicago, in which the alanine is replaced by an aspartic acid. Its functional properties are similar to those of Hb A [5]. The second is Hb Calais, which was found in a patient presenting with a chronic cyanosis [6]. In this case the alanine residue was replaced by a proline, resulting in a normally stable Hb but with decreased oxygen binding properties. From studies performed on bovine Hb, residue β76(E20) that is a lysine in these animals, seems to be an additional chloride-dependent regulatory site partly responsible for the decreased oxygen affinity [7]. In Hb Harlequin, the change from an alanine to a valine, is not expected to grossly alter the oxygen binding properties.

     

Fig. 3. Series of ions obtained by MS/MS analysis of the abnormal peptide (566.8 3+). The Y series of ions, from Y7 to Y14, have a value increased by 28 as compared to the normal, in agreement with the replacement of alanine 76 by a valine.

 The chromatographic behavior of Hb Harlequin is somewhat surprising. In the reversed phase HPLC system that we use, the b chain of Hb Harlequin was eluted together with bA. This differs drastically from what is observed for the b chain of Hb La Desirade [β129(H7) AlaŚ>Val], in which an identical amino acid exchange occurs. In an arbitrary scale, where bA elutes at 10 and a at 20, the β chain of Hb La Desirade elutes within the 15.1-15.5 window [2]. In contrast, the expected increase in hydrophobicity was found when the abnormal tryptic peptide was isolated by reversed phase HPLC. A possible explanation could be that the region of the Hb molecule around position E20 contains several charged residues [Asp 73 (E17), His 77 (EF1) and Asp 79 (EF3)] that may shield the alanine as well as the valine. The behavior of Hb Harlequin during ion exchange HPLC is also surprising. It is likely that minimal changes in the geometry of this area may alter the distribution of charges at the surface, and thus, their interactions with the cation exchange phase.

Fig. 4. Three dimensional representation of Hb Harlequin showing the localization of the substitution at the exterior of the molecule, near to the central cavity.




Number 22
VOL. 22, 2019 Accepted articles
Number 22
VOL. 22, 2019 Supplement
Number 21
VOL. 21(2), 2018
Number 21
VOL. 21 (1), 2018
Number 21
VOL. 21, 2018 Accepted articles
Number 21
VOL. 21, 2018 Supplement
Number 20
VOL. 20 (2), 2017
Number 20
VOL. 20 (1), 2017
Number 19
VOL. 19 (2), 2016
Number 19
VOL. 19 (1), 2016
Number 18
VOL. 18 (2), 2015
Number 18
VOL. 18 (1), 2015
Number 17
VOL. 17 (2), 2014
Number 17
VOL. 17 (1), 2014
Number 16
VOL. 16 (2), 2013
Number 16
VOL. 16 (1), 2013
Number 15
VOL. 15 (2), 2012
Number 15
VOL. 15, 2012 Supplement
Number 15
Vol. 15 (1), 2012
Number 14
14 - Vol. 14 (2), 2011
Number 14
The 9th Balkan Congress of Medical Genetics
Number 14
14 - Vol. 14 (1), 2011
Number 13
Vol. 13 (2), 2010
Number 13
Vol.13 (1), 2010
Number 12
Vol.12 (2), 2009
Number 12
Vol.12 (1), 2009
Number 11
Vol.11 (2),2008
Number 11
Vol.11 (1),2008
Number 10
Vol.10 (2), 2007
Number 10
10 (1),2007
Number 9
1&2, 2006
Number 9
3&4, 2006
Number 8
1&2, 2005
Number 8
3&4, 2004
Number 7
1&2, 2004
Number 6
3&4, 2003
Number 6
1&2, 2003
Number 5
3&4, 2002
Number 5
1&2, 2002
Number 4
Vol.3 (4), 2000
Number 4
Vol.2 (4), 1999
Number 4
Vol.1 (4), 1998
Number 4
3&4, 2001
Number 4
1&2, 2001
Number 3
Vol.3 (3), 2000
Number 3
Vol.2 (3), 1999
Number 3
Vol.1 (3), 1998
Number 2
Vol.3(2), 2000
Number 2
Vol.1 (2), 1998
Number 2
Vol.2 (2), 1999
Number 1
Vol.3 (1), 2000
Number 1
Vol.2 (1), 1999
Number 1
Vol.1 (1), 1998

 

 


 About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact
 Copyright © Balkan Journal of Medical Genetics 2006