title: Family study of a Swiss patient uncovered a novel genetic basis for the S-s-U+(var) phenotype.
abstract: BACKGROUND
  The rare S-s- phenotype is typically found in persons of African origin. Three genetic bases underlying this phenotype have been identified so far: a large deletion including the GYPB gene, which encodes the S and s antigens, and two mutations affecting GYPB splicing (commonly called "P2" and "NY"). The discovery of the S-s- phenotype in a Swiss patient prompted this study.
  
  
  METHODS
  The GYPB genotype of the patient was analyzed with Beadchip technology and Sanger sequencing. GYPB haplotype analysis was also carried out in the patient's family. A functional splicing assay was developed to determine the impact of the identified mutation on GYPB splicing.
  
  
  RESULTS
  Sanger sequencing of GYPB in the patient indicated that she was homozygous for a GYPB*s allele carrying a novel mutation in the splice donor site of Intron 5 (c.270+5G>A). Analysis of GYPB haplotypes in the patient's family revealed that she actually inherited this mutated GYPB*s allele from her mother of Swiss ancestry and a deleted GYPB allele from her father of Egyptian ancestry. Using a minigene-based splicing assay, we showed that GYPB mutation c.270+5G>A causes the skipping of Exon B5, as previously reported for the P2 mutation (c.270+5G>T). Consistently, the patient's red blood cells were found to be S-s-U+(var) .
  
  
  CONCLUSIONS
  A novel GYPB mutation (c.270+5G>A) accounting for the S-s-U+(var) phenotype was identified. In contrast with P2 and NY mutations, which also drive this rare phenotype, this novel GYPB mutation inactivates a GYPB*s allele and does not appear to be of African origin.
authors.affiliation: National Institute of Blood Transfusion (INTS), Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Saison
authors.forename: Sophie
authors.initials: S
authors.lastname: Waldvogel
authors.forename: Dominique
authors.initials: D
authors.lastname: Gien
authors.forename: Thierry
authors.initials: T
authors.lastname: Peyrard
authors.forename: Lionel
authors.initials: L
authors.lastname: Arnaud
mesh_terms: D000328:Adult; D000483:Alleles; D001789:Blood Group Antigens / Q000235:genetics*; D021983:Cyclophilins / Q000235:genetics*; D004912:Erythrocytes; D005091:Exons; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D017354:Point Mutation; D022821:RNA Splice Sites; D013557:Switzerland
chemical_list: D001789:Blood Group Antigens; D022821:RNA Splice Sites; C081786:cyclophilin B; D021983:Cyclophilins