A new AQP1 null allele identified in a Gypsy woman who developed an anti‐CO3 during her first pregnancy

Abstract

Background and Objectives The Colton blood group antigens are carried by the AQP1 water channel. AQP1−/− individuals, also known as Colton-null since they express no Colton antigens, do not suffer any apparent clinical consequence but may develop a clinically significant alloantibody (anti-CO3) induced by transfusion or pregnancy. Identification and transfusion support of Colton-null patients are highly challenging, not only due to the extreme rarity of this phenotype, the lack of appropriate reagents in most laboratories, as well as the possibility of confusing its with the recently described CO:-1,-2,3,-4 phenotype where AQP1 is present. This study investigated a new Colton-null case and evaluated three commercially available anti-AQP1s to identify Colton-null red blood cell samples. Methods The Colton-null phenotype was investigated by standard serological techniques, AQP1 sequencing, immunoblot and flow cytometry analyses. Results We identified and characterized the Colton-null phenotype in a Gypsy woman who developed an anti-CO3 during her first pregnancy. After developing a simple and robust method to sequence AQP1, we showed that she was apparently homozygous for a new AQP1 null allele, AQP1 601delG, whose product is not expressed in her red blood cells. We also established the Colton specificity of three commercially available anti-AQP1s in immunoblot and/or flow cytometry analyses. Conclusion This Gypsy woman represents the sixth Colton-null case characterized at the serological, genetic and biochemical levels. The validation here of new reagents and methods should facilitate the identification of Colton-null individuals.

Energetic and Molecular Water Permeation Mechanisms of the Human Red Blood Cell Urea Transporter B

“…RBCs from two individuals of the AQP1null rare phenotype lacking AQP1 (also called Colton-null because AQP1 carries Colton antigens) donated in 1994 have been described [26] , [27] . Control RBCs and RBCs from one Rhnull and three independent UT-Bnull individuals were cryopreserved since 1991 and 2003 respectively in the rare blood collection at the Centre National de Référence des Groupes Sanguins (Paris, France).…”

An AQP1 allele associated with Co(a–b–) phenotype

“…While this paper was under review, the same allele was found in a Gypsy family; this AQP1 null CO*A(601delG) allele 16 is provisionally designated CO*01N.06 and joins five other silencing null alleles that have been characterized for AQP1 to date.…”