title: A simple screening assay for the most common JK*0 alleles revealed compound heterozygosity in Jk(a-b-) probands from Guam.
abstract: The Jk(a-b-) phenotype results from alterations in the JK gene and is characterized by absence of the RBC urea transporter in the cell membrane. The frequency of Jk(a-b-) varies among populations,but this phenotype is most commonly found in people of Polynesian and Finnish descent. Although rare, Jk(a-b-) individuals present a clinical challenge because anti-Jk3 is produced readily in response to transfusion and pregnancy, and Jk(a-b-) blood is not routinely available. Identification of Jk(a-b-) patients and donors is most often performed serologically. However, ten JK*0 alleles have been identified, and this information can be used in DNA-based typing. We selected five JK*0 alleles that had been encountered by our reference laboratory in two or more samples from unrelated individuals and designed an allele-specific primer PCR assay for use as an initial screening tool. After in-house validation,we tested genomic DNA from a family: a mother and her two sons referred to us for genetic investigation of their Jk(a-b-)phenotypes. Two different nucleotide substitutions, -1g>a in intron 5 (IVS5) and 956C>T in exon 10, originally associated with Polynesian and Indian/African populations respectively, were identified in the family. The mother and one son were compound heterozygotes, and the second son was homozygous for IVS5-1g>a. We conclude that the effort to design and validate such a screening assay was cost-efficient when compared with DNA sequencing costs. Furthermore, selection of the more common JK*0 mutations was a practical approach that resulted in rapid identification of the genetic bases behind the Jk(a-b-) phenotypes in this unusual family. Although an obvious target for eventual inclusion into high-throughput genotyping platforms for clinical diagnostic services, current systems are very limited. Our approach provides a simple and inexpensive method for the identification of these rare alleles.
authors.affiliation: Nordic Reference Laboratory for Blood Group Genomic Typing, Clinical Immunology and Transfusion Medicine, University and Regional Laboratories, Lund, Sweden.
authors.forename: E S
authors.initials: ES
authors.lastname: Wester
authors.forename: J
authors.initials: J
authors.lastname: Gustafsson
authors.forename: B
authors.initials: B
authors.lastname: Snell
authors.forename: P
authors.initials: P
authors.lastname: Spruell
authors.forename: A
authors.initials: A
authors.lastname: Hellberg
authors.forename: M L
authors.initials: ML
authors.lastname: Olsson
authors.forename: J R
authors.initials: JR
authors.lastname: Storry
mesh_terms: D000906:Antibodies / Q000097:blood; D001787:Blood Group Incompatibility / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D006141:Guam; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D026901:Membrane Transport Proteins / Q000172:deficiency / Q000276:immunology; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D011110:Polymorphism, Genetic; D000096982:Urea Transporters
chemical_list: D000906:Antibodies; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; D000096982:Urea Transporters; C522691:RETREG1 protein, human