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

Summary, in English

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: Jill Storry; Marion E Reid; Susan Fetics; Cheng-Han Huang
• Publishing year: 2003
• Language: English
• Pages: 1738-1747
• Publication/Series: Transfusion
• Volume: 43
• Issue: 12
• Links: http://dx.doi.org/10.1046/j.0041-1132.2003.00585.x
• Document type: Journal article
• Publisher: Wiley-Blackwell
• Topic: Hematology
• Status: Published
• ISBN/ISSN/Other: ISSN: 1537-2995