Two novel Jknull alleles derived from 222C>A in Exon 5 and 896G>A in Exon 9 of the JK gene

BACKGROUND: Polynesian Jknull is well known for its mutation as Intron 5 g>a at the 3′ splice acceptor site. After sequencing analysis, however, it was noticed that only three of eight samples with the Jknull phenotype carried typical homozygous Polynesian Jknull mutation. Five others were noted to be unreported heterozygous Polynesian Jknull mutation. An investigation was then conducted to characterize the underlying mechanism leading to this particular Jknull genotype. STUDY DESIGN AND METHODS: Genomic DNA covering 5′-untranslated region exons and intervening introns of the JK gene was amplified by polymerase chain reaction, and the fragments were directly sequenced. The sequencing results were compared with those published in literature and related biologic Web sites. RESULTS: In all five samples with a heterozygous Polynesian Jknull mutation, additional mutations were identified. Two samples carried missense mutations: 222C>A (Asn74Lys) in Exon 5 and 499A>G (Met167Val) in Exon 7. Three others had missense mutation 896G>A (Gly299Glu) in Exon 9. These substituted amino acids were located either near or at transmembrane domains, respectively. In addition, two polymorphic nucleotides at positions −103 (a>g) and −119(c>a) from the 3′ end of Intron 1 were also Polynesian mutation–related. CONCLUSIONS: In contrast to the typical homozygous Polynesian Jknull mutation, two novel heterozygous Jknull alleles were noted to be associated with the Jknull phenotype. One carried missense mutation 222C>A in Exon 5, and the other had 896G>A missense mutation in Exon 9. These findings may have implications in designing a molecular screening assay for people with the Jknull phenotype.