title: A common ancestral glycoprotein (GP) 9 1828A>G (Asn45Ser) gene mutation occurring in European families from Australia and Northern Europe with Bernard-Soulier Syndrome (BSS).
abstract: Bernard-Soulier syndrome (BSS) is an extremely rare hereditary bleeding disorder, caused by mutations occurring in the Glycoprotein (GP) Ibalpha, GPIbbeta and GP9 genes that encode for the corresponding subunits of platelet GPIb-V-IX adhesion receptor complex. BSS has been reported in many populations, mostly behaving in an autosomal-recessive manner.While the great majority of BSS mutations are unique to a single individual or family, the GP9 1828A>G Asn45Ser mutation, which we have identified in an undocumented Australian Caucasian, has already been reported in multiple unrelated Caucasian families from various Northern and Central European countries. Haplotype analysis of 19 BSS patients from 15 unrelated Northern European families (including 2 compound heterozygote siblings from a British family previously published, and 17 1828A>G Asn45Ser homozygotes), showed that 14 of these BSS patients from 11 of the 1828A>G Asn45Ser homozygote families share a common haplotype at the chromosomal region 3' to the GP9 gene. Hence, the results suggest that the GP9 1828A>GAsn45Ser mutation in these families is ancient, and its frequent emergence in the European population is the result of a founder effect rather than recurrent mutational events. Association of the 1828A>G Asn45Ser mutation with variant haplotypes in 4 other Northern European BSS families raised the possibility of a second founder event, or rare recombinations in these families. Additional members from these 'atypical' lineages would need to be screened to resolve this question.
authors.affiliation: Northern Blood Research Centre, Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, St Leonards, Australia. hliang@med.usyd.edu.au
authors.forename: Hai Po Helena
authors.initials: HP
authors.lastname: Liang
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Morel-Kopp
authors.forename: Jeannine M
authors.initials: JM
authors.lastname: Clemetson
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Clemetson
authors.forename: Riitta
authors.initials: R
authors.lastname: Kekomaki
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kroll
authors.forename: Katerina
authors.initials: K
authors.lastname: Michaelides
authors.forename: Edward G D
authors.initials: EG
authors.lastname: Tuddenham
authors.forename: Karen
authors.initials: K
authors.lastname: Vanhoorelbeke
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Ward
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001315:Australia / Q000208:ethnology; D001606:Bernard-Soulier Syndrome / Q000208:ethnology / Q000235:genetics*; D005060:Europe / Q000453:epidemiology / Q000208:ethnology; D019143:Evolution, Molecular; D018703:Founder Effect; D006239:Haplotypes; D040941:Heredity; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009154:Mutation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D013997:Time Factors
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex