title: New mutations on platelet GPIIb in Sub-Saharan African populations revealed by genotyping discrepancies.
abstract: BACKGROUND
  Previous studies of platelet allele frequencies in Sub-Saharan African populations enabled us to identify discrepancies in HPA-3 typing, suggesting the presence of new mutations and of a greater polymorphism than so far described in other populations.
  
  
  OBJECTIVE
  To analyze these discrepancies and to assess the factors leading to potential alloimmunization in these populations.
  
  
  METHODS
  
  
  
  METHODS
  Maternal samples from a Beninese woman following in utero death and panels of blood donors from Benin, Cameroon, Congo, and Pygmies from Central Africa.
  
  
  METHODS
  Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), PCR-sequence specific primers (PCR-SSP) and sequencing techniques.
  
  
  RESULTS
  Three new mutations were found on GPIIb gene: exon 26 a) 2614C>A situated between HPA-3 and HPA-9w, b) 2645C>T downstream of HPA-3, c) intron 26 IVS26+89G>A. These mutations may lead to discrepant DNA typing results, due either to a localization in the complementary sequence recognized by the primer or to the appearance of a new enzyme restriction site. Furthermore, a bilateral linkage << deletion (Delta9 bp) intron 21 and the HPA-3b allele (exon 26) >> found in Caucasian, Asian, and Oceanian populations is not found in African populations, suggesting that its appearance was prior to HPA-3.
  
  
  CONCLUSIONS
  Three new mutations have been identified, two of them potentially immunogenic through their position. Furthermore, the polymorphism found on intron 26, localized in the complementary sequence of the PCR primer, may lead to a false typing assignation. It is therefore important to diversify techniques, both genomic (PCR-RFLP and PCR-SSP), and proteomic monoclonal antibody-specific immobilization of platelets antigen (MAIPA) to ensure accurate HPA antigenic system typing.
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Hallé
authors.forename: V
authors.initials: V
authors.lastname: Jallu
authors.forename: G
authors.initials: G
authors.lastname: Mulen-Imandy
authors.forename: A
authors.initials: A
authors.lastname: Bigot
authors.forename: K
authors.initials: K
authors.lastname: M'bayo
authors.forename: L Y
authors.initials: LY
authors.lastname: Anani
authors.forename: C
authors.initials: C
authors.lastname: Kaplan
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D001541:Benin; D044383:Black People / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism*; D002163:Cameroon; D003223:Congo; D004252:DNA Mutational Analysis; D005260:Female; D005315:Fetal Diseases / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000276:immunology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D040201:Platelet Membrane Glycoprotein IIb / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D013921:Thrombocytopenia / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000276:immunology
chemical_list: D040201:Platelet Membrane Glycoprotein IIb