Two novel null alleles of the KEL gene detected in two Chinese women with the K_null phenotype

Abstract

In screening 87665 unrelated healthy blood donors in China, serology studies resulted in the detection of two K(0) probands, both female. To explore the molecular basis of the K(null) phenotype in the Chinese population, genomic DNA, total RNA, and reticulocyte RNA were subsequently prepared from the two probands, five family members of proband 1, four unrelated normal controls, and one unrelated KEL1 control. Nucleic acids were analyzed for the KEL gene by DNA and RNA sequencing, while antigens were analyzed by flow cytometry with BRIC18, BRIC68, anti-k, and anti-Kp(b). Two novel K(null) alleles were identified in both probands: in exon 3, 185insT (Ser62Phe and a premature stop codon in exon 4, GenBank accession number, EF208900), and in exon 7, 715G>T (Glu239Stop, GenBank accession number EF208901). Alternative splicing patterns were observed in RNA obtained from whole blood versus from a reticulocyte fraction. Our study identified these two novel K(null) alleles resulting in the K(null) phenotype, the frequency of the K(null) phenotype amongst Chinese mainlanders is only 0.00228%.

Molecular Basis of KELnull Phenotype in Brazilians

“…Therefore, it is a real challenge to accurately measure the frequency of this phenotype even in populations with similar genetic background. Recent data reported that the K₀ frequency is expected to be 0.00228% in Chinese [26] and no more than 0.00017% in Austrian population [25]. These latest findings showed much lower frequencies than previously estimated in Europeans and Japanese of 0.007% and 0.008%, respectively [34].…”

“…There are also a few examples of nucleotide insertion or deletion, and 7 cases of missense mutation [5,6,21,22,23,24,25,26,27,28,29,30]. Table 3 lists the known K 0 alleles.…”

“…At present, 37 K 0 alleles are recognized to abolish the KEL antigens expression, most of them due to stop codon and alternative splicing caused by single nucleotide mutation. These mutations have been detected in different populations reported by Asian, European and North American studies nevertheless none performed in Amerindian-Caucasian descendants from South America [5,6,21,22,23,24,25,26,27,28,29,30]. In this paper, we reported the IVS16 + 1g>a mutation ( KEL*02N.31 allele) and the c.1042C>T mutation ( KEL*02N.04 allele) in three Brazilian K₀ patients being descendants of Amerindian-Caucasians.…”

Identification of novel silent KEL alleles causing KEL:−5 (Ko) phenotype or discordance between KEL:1,−2 phenotype/KEL*01/02 genotype

“…The very rare KEL:–5 phenotype has been shown to result from silent KEL genes, also called KEL null alleles, present at the homozygous state or in compound heterozygosity. To date, more than 10 different KEL null alleles have been described …”

Silent KEL alleles identified from Japanese individuals with the Ko phenotype

“…in 1957 . The incidence of the K o phenotype has been reported as 0·003% (2 in 63 700) in the Japanese population , which is an intermediate value between 0·0028% (2 in 87 665) in the Chinese population and 0·004% in Caucasians . Anti‐Ku is against a high prevalence antigen and is produced by immunized K o individuals and causes haemolytic disease of foetus and newborn as well as the severe and fatal haemolytic transfusion reaction .…”