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

Abstract：

BACKGROUND AND OBJECTIVES: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. METHODS:Seventy-five blood samples with a weak D phenotype were detected from 763 408 blood donors by standard serological methods. Forty-five of the 75 blood donors were available for RHD gene analysis by PCR and sequencing using genomic DNA and reticulocyte mRNA. Real-time PCR was performed to estimate the relative amounts of the RHD transcripts. RESULTS:We detected 16 different RHD alleles in the 45 individuals with weak D by nucleotide sequencing; 12 were newly identified. Thirty-two of the 45 individuals had an RHD allele with a single missense mutation, while the other 13 individuals had RHD with a c.960G>A silent mutation in exon 7. Red blood cells of these 13 individuals showed direct agglutination with anti-D at a strength of 3+ or less. Semi-quantitative analysis of the RHD transcripts by real-time PCR revealed that the cDNA samples with the c.960G>A mutation showed a significant increment of exon 7 skipping compared with the common RHD. CONCLUSION:Reduced expression of D antigen is caused not only by missense mutation of the RHD gene, but also by silent mutation that may affect splicing.

journal_name

Vox Sang

journal_title

Vox sanguinis

authors

Ogasawara K,Sasaki K,Isa K,Tsuneyama H,Uchikawa M,Satake M,Tadokoro K

doi

10.1111/vox.12322

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

179-84

issue

2

eissn

0042-9007

issn

1423-0410

journal_volume

110

pub_type

杂志文章

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