A novel mutation at the JK locus causing Jknull phenotype in a Chinese family

Abstract

Urea transporters are a group of proteins that facilitate urea movement across biological membranes. Kidd blood group (Jk antigen) and urea transporter of human erythrocytes are carried by the same protein UT-B. To investigate the molecular basis of the Jk null phenotype in the Chinese population, blood samples from Chinese individuals were screened using the 2 mol/L urea solution hemolysis test. Urea and water permeability of erythrocytes membrane was measured by stopped-flow light scattering. Genomic DNA was extracted from lymphocytes. UT-B gene of JKnnu's family was analyzed using genomic PCR by primers designed to cover sequences of all exons and exon-intron boundaries in human UT-B gene. One Jk null subject was found from twenty thousand screened Chinese individuals, and it was confirmed that this individual did not express the erythrocyte urea transporter. Genomic sequence analysis of the Jk null individual showed that there were two point mutations, G-->C, which is novel, and G-->A, at the 3'-acceptor splice site (AG) of intron 5 of UT-B gene. Exon 6 is spliced out in the UT-B transcript due to either of these mutations. Water permeability in Jk null erythrocytes (Pf, -0.00037 cm/s) was significantly lower than that in normal erythrocytes (Pf, -0.00062 cm/s) after HgCl2 incubation, providing evidence for UT-B facilitated water transport in human erythrocytes.

Surface electrocardiogram and action potential in mice lacking urea transporter UT-B

“…UT-B protein expressed in the human erythrocyte is identified as the Jk antigen [5] . Jk (a-b-) (Jk null ) humans, who are very rare, have a mild urine-concentrating defect [6,7] . It has not been reported that Jk null individuals are associated with any other clinical syndrome.…”

Red blood cell genotyping in China

“…This rare phenotype has been reported with the highest frequency in Polynesians (0·1–1·4%). In the Chinese populations, the frequency of JK(a‐b‐) in the southern regions is about 1:5000 (10/50 000 in Guangzhou), which is higher than some other reported regions (1:20 000 in Changchun ; 1:25 000 (4/102 760 and 2/48 400) in Shanghai ; 1:17000–1:20 000 (3/52 260 to 2/40 337 ) in Nanjing; not found (0/23 909) in Zhejiang ) using the red blood cell urea lysis resistance assay for screening. Several patients with anti‐Jk3 were also encountered in Guangzhou .…”

Structure of Urea Transporters

“…The permeation of water through UT-B, although initially controversial (Martial et al 1996; Sidoux-Walter et al 1999), has since been well established (Yang and Verkman 1998; Yang and Verkman 2002; Meng et al 2005). Recent estimates of the rate of water permeation through UT-B are similar to those measured for aquaporins (Azouzi et al 2013).…”