Hatsue Tsuneyama

A new blood group system, RHAG: three antigens resulting from amino acid substitutions in the Rh-associated glycoprotein

Background and Objectives  Rh‐associated glycoprotein (RhAG) is closely associated with the Rh proteins in the red cell membrane. Two high frequency antigens (Duclos and DSLK) and one low frequency antigen (Ola) have serological characteristics suggestive of expression on RhAG.

Polymorphisms of RhDVa and a New RhDVa–Like Variant Found in Japanese Individuals

Background and Objectives: Red cell type RhDVa lacks epD1 and 5 and is encoded by hybrid RHD–CE(5)–D alleles. We analyzed RhDVa and RhDVa–like samples in Japanese blood donors. Materials and Methods: Ten RhDVa samples lacked epD1 and 5 and 3 RhDVa–like variants also lacked, epD2 and a part of 6/7. We identified the full–length nucleotide sequences of the complementary DNA (cDNA) synthesized from 4 samples: 3 of type DVa and the 4th a DVa–like variant. Results: Although their sequences differed from each other, all the substitutions were exclusively in exon 5. Three DVa samples had hybrid RHD–CE(5)–D alleles, but the DVa–like variant had a unique nucleotide substitution with a single amino acid change, E233K. Exon 5 of the genomic DNA from all 13 samples was analyzed by sequencing. No other sequences were identified. Conclusion: All RhDVa and RhDVa–like variants had the substitution for E233. E233 seems to be a determinant of epD1 and 5. A new category of RhD variant, DYO, was identified.

E variants found in Japanese and c antigenicity alteration without substitution in the second extracellular loop

BACKGROUND: The molecular basis of E variants in the Japanese population is poorly understood. In this study, molecular analysis of E variants detected in Japanese by serologic methods was carried out.

Deletion of the RUNX1 binding site in the erythroid cell-specific regulatory element of the ABO gene in two individuals with the Am phenotype.

An erythroid cell‐specific regulatory element, referred to as the +5·8‐kb site, had been identified in the first intron of the human ABO blood group gene. Subsequent studies revealed that either a 5·8‐kb deletion including the +5·8‐kb site or disruption of a GATA factor binding motif at the site was present in all Bm and ABm individuals examined. We investigated the molecular mechanism of the Am phenotype, which is analogous to the Bm phenotype.

Molecular basis for D− Japanese: identification of novel DEL and D− alleles

The occurrence of D− is approximately 0·5% in Japanese, but DEL in apparently D− individuals is relatively common compared with that in Caucasian populations. On the basis of molecular genetics, we examined D− Japanese blood donors.

JK null alleles identified from Japanese individuals with Jk(a−b−) phenotype

The Kidd blood group system consists of three common phenotypes: Jk(a+b−), Jk(a−b+) and Jk(a+b+), and one rare phenotype, Jk(a−b−). Jka/Jkb polymorphism is associated with c.838G>A (p.Asp280Asn) in exon 9 of the JK (SLC14A1) gene, and the corresponding alleles are named JK*01 and JK*02. The rare phenotype Jk(a−b−) was first found in a Filipina of Spanish and Chinese ancestry, and to date, several JK null alleles responsible for the Jk(a−b−) phenotype have been reported. We report seven novel JK null alleles, 4 with a JK*01 background and 3 with a JK*02 background, identified from Jk(a−b−) Japanese.

Presence of nucleotide substitutions in transcriptional regulatory elements such as the erythroid cell-specific enhancer-like element and the ABO promoter in individuals with phenotypes A3 and B3, respectively

An erythroid cell‐specific regulatory element, referred to as the +5.8‐kb site, has been identified in the first intron of the human ABO blood group gene. Subsequent studies have revealed involvement of deletion or mutation at the site in phenotypes Am, Bm and ABm. We investigated the molecular mechanisms involved in the A3 and B3 phenotypes.

First case of hemolytic disease of the newborn due to anti-Ula antibodies.

The first case of hemolytic disease of the newborn (HDN) due to anti‐Ula antibodies is described. The infant had severe anemia with a positive direct antiglobulin test with anti‐IgG that required blood transfusion. But jaundice was not severe enough for exchange transfusion or phototherapy.

Weak D alleles in Japanese: a c.960G>A silent mutation in exon 7 of the RHD gene that affects D expression

The molecular basis of the weak D phenotype has been investigated for many years, and more than 80 different alleles producing weak D phenotypes have been identified. Most alleles producing weak D phenotypes have a single missense mutation in exons corresponding to a transmembrane domain of the RhD polypeptide. We report here RHD alleles with single nucleotide mutations in Japanese accounting for weak expression of D antigen.

Mutations of the KLF1 gene detected in Japanese with the In(Lu) phenotype

In(Lu) is characterized by a reduced expression of antigens in the Lutheran blood group system as well as other blood group antigens. Mutations of the erythroid transcription factor, KLF1, have been reported to cause the In(Lu) phenotype, and we investigated Japanese In(Lu) to estimate the prevalence of the phenotype and KLF1 polymorphism.