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Vox Sang. 2016 Feb;110(2):179-84. doi: 10.1111/vox.12322. Epub 2015 Sep 4.

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

Author information

1
Japanese Red Cross Central Blood Institute, Tokyo, Japan.
2
Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan.

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.

KEYWORDS:

RHD gene; Rh blood group; exonic splicing regulator; silent mutation; weak D

PMID:
26340140
DOI:
10.1111/vox.12322
[Indexed for MEDLINE]

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