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Mutations in GYPB exon 5 drive the S-s-U+(var) phenotype in persons of African descent: implications for transfusion

Storry, Jill LU ; Reid, Marion E; Fetics, Susan and Huang, Cheng-Han (2003) In Transfusion 43(12). p.1738-1747
Abstract
BACKGROUND: The S-s-U- phenotype in African Americans is due to a GYPB deletion, however the molecular basis for the S-s-U+var phenotype is poorly understood. Variable reactivity of S-s-U+var RBCs with monoclonal anti-He or by anti-U has been demonstrated, however the underlying molecular bases for this phenotype remain to be established. STUDY DESIGN AND METHODS: Hemagglutination was performed on 104 S-s- blood samples using monoclonal anti-He and anti-U. GYPB was sequenced from selected samples. Allele and exon-specific PCR analysis was used to identify wild-type and mutant alleles. RESULTS: The RBCs of 49-percent S-s- samples were identified as S-s-U+var by hemagglutination. Sequencing analysis of 41 samples revealed 1) a point mutation... (More)
BACKGROUND: The S-s-U- phenotype in African Americans is due to a GYPB deletion, however the molecular basis for the S-s-U+var phenotype is poorly understood. Variable reactivity of S-s-U+var RBCs with monoclonal anti-He or by anti-U has been demonstrated, however the underlying molecular bases for this phenotype remain to be established. STUDY DESIGN AND METHODS: Hemagglutination was performed on 104 S-s- blood samples using monoclonal anti-He and anti-U. GYPB was sequenced from selected samples. Allele and exon-specific PCR analysis was used to identify wild-type and mutant alleles. RESULTS: The RBCs of 49-percent S-s- samples were identified as S-s-U+var by hemagglutination. Sequencing analysis of 41 samples revealed 1) a point mutation at +5 (g > t) of intron 5 that resulted in skipping of exon 5 in 34 samples; 2) two mutations (208G > T and 230C > T) caused partial skipping of exon 5 in four samples due to activation of a cryptic 3' splice site that resulted from a C > G transversion at nt251 present in all GYPB*S alleles and most GYPB*s alleles tested. Three samples were heterozygous for the mutated alleles. DISCUSSION: The S-s-U+var phenotype arises from changes in or around GYPB exon 5. The weak expression of U and in most examples, He, may be due to low levels of normal transcription of the variant gene or to posttranscriptional down regulation. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Transfusion
volume
43
issue
12
pages
1738 - 1747
publisher
Wiley-Blackwell
external identifiers
  • pmid:14641872
  • scopus:0344303481
ISSN
1537-2995
DOI
10.1046/j.0041-1132.2003.00585.x
language
English
LU publication?
no
id
330a39dc-653a-43a7-9096-3b54c3bc18df (old id 1126492)
date added to LUP
2008-06-11 10:30:34
date last changed
2018-01-07 09:34:20
@article{330a39dc-653a-43a7-9096-3b54c3bc18df,
  abstract     = {BACKGROUND: The S-s-U- phenotype in African Americans is due to a GYPB deletion, however the molecular basis for the S-s-U+var phenotype is poorly understood. Variable reactivity of S-s-U+var RBCs with monoclonal anti-He or by anti-U has been demonstrated, however the underlying molecular bases for this phenotype remain to be established. STUDY DESIGN AND METHODS: Hemagglutination was performed on 104 S-s- blood samples using monoclonal anti-He and anti-U. GYPB was sequenced from selected samples. Allele and exon-specific PCR analysis was used to identify wild-type and mutant alleles. RESULTS: The RBCs of 49-percent S-s- samples were identified as S-s-U+var by hemagglutination. Sequencing analysis of 41 samples revealed 1) a point mutation at +5 (g > t) of intron 5 that resulted in skipping of exon 5 in 34 samples; 2) two mutations (208G > T and 230C > T) caused partial skipping of exon 5 in four samples due to activation of a cryptic 3' splice site that resulted from a C > G transversion at nt251 present in all GYPB*S alleles and most GYPB*s alleles tested. Three samples were heterozygous for the mutated alleles. DISCUSSION: The S-s-U+var phenotype arises from changes in or around GYPB exon 5. The weak expression of U and in most examples, He, may be due to low levels of normal transcription of the variant gene or to posttranscriptional down regulation.},
  author       = {Storry, Jill and Reid, Marion E and Fetics, Susan and Huang, Cheng-Han},
  issn         = {1537-2995},
  language     = {eng},
  number       = {12},
  pages        = {1738--1747},
  publisher    = {Wiley-Blackwell},
  series       = {Transfusion},
  title        = {Mutations in GYPB exon 5 drive the S-s-U+(var) phenotype in persons of African descent: implications for transfusion},
  url          = {http://dx.doi.org/10.1046/j.0041-1132.2003.00585.x},
  volume       = {43},
  year         = {2003},
}