title: Compound heterozygosity for a novel nine-nucleotide deletion and the Asn45Ser missense mutation in the glycoprotein IX gene in a patient with Bernard-Soulier syndrome.
abstract: Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder due to quantitative or qualitative abnormalities in the platelet glycoprotein (GP) Ib/IX/V complex, the major von Willebrand factor receptor. The complex comprises four subunits, each encoded by a separate gene. Several mutations have been described for each of the subunits, except for GPV, as a cause of BSS. We describe here the genetic basis of the disorder in a child with BSS. Flow-cytometric analysis of the patient's platelets showed a markedly reduced surface expression of all three glycoproteins of the GPIb/IX/V complex. DNA sequencing analysis showed the patient to be a compound heterozygote for two mutations in the GPIX gene, a novel nine-nucleotide deletion starting at position 1952 of the gene that changes asparagine 86 for alanine and eliminates amino acids 87, 88, and 89 (arginine, threonine, and proline) and a previously reported point mutation that changes the codon asparagine (AAC) for serine (AGC) at residue 45. Her mother was heterozygous for the Asn45Ser mutation, and her father, for the nine-nucleotide deletion. Our findings suggest that the additive effects of both mutations in the GPIX gene are responsible for the BSS phenotype of the patient.
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Drouin
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Carson
authors.forename: Odette
authors.initials: O
authors.lastname: Laneuville
mesh_terms: D001216:Asparagine; D001483:Base Sequence; D001606:Bernard-Soulier Syndrome / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004247:DNA / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D020125:Mutation, Missense; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics* / Q000378:metabolism; D012694:Serine
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; D012694:Serine; D001216:Asparagine; D004247:DNA