title: A novel homozygous 8-base pair deletion mutation in the glycoprotein Ibalpha gene in a patient with Bernard-Soulier syndrome.
abstract: We present a patient with Bernard-Soulier syndrome harboring a novel mutation. Flow cytometric analysis showed that the glycoprotein (GP) Ib/IX complex was absent from the platelet surface. By immunoblotting, GPIbalpha, GPIbbeta and GPIX were not detected in the platelet lysates. Glycocalicin, the soluble GPIbalpha fragment, was also absent in the plasma. Genetic analysis revealed a novel homozygous 8-base pair deletion in the GPIbalpha gene, 1136_1143delTTCACATG, which was predicted to cause a frame shift and the addition of 13 altered amino acids followed by premature termination. No mutation was found in the coding sequence of the GPIbbeta or GPIX genes. We demonstrated that the novel deletion mutation resulted in complete defectiveness of the GPIbalpha protein and null expression of the entire GPIb/IX complex, and was responsible for the Bernard-Soulier syndrome phenotype in this patient. Although the presence of a truncated GPIbalpha protein has been often documented, complete absence of the protein has been scarcely reported in Bernard-Soulier syndrome patients with a GPIbalpha mutation causing a premature stop codon. An underlying molecular mechanism to explain how the synthesis of a truncated protein is inhibited in selected cases remains to be elucidated.
authors.affiliation: Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. chihaya@med.niigata-u.ac.jp
authors.forename: Chihaya
authors.initials: C
authors.lastname: Imai
authors.forename: Shinji
authors.initials: S
authors.lastname: Kunishima
authors.forename: Takayuki
authors.initials: T
authors.lastname: Takachi
authors.forename: Haruko
authors.initials: H
authors.lastname: Iwabuchi
authors.forename: Tae
authors.initials: T
authors.lastname: Nemoto
authors.forename: Masaru
authors.initials: M
authors.lastname: Imamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchiyama
mesh_terms: D000595:Amino Acid Sequence; D001606:Bernard-Soulier Syndrome / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004200:Diseases in Twins; D004844:Epistaxis / Q000209:etiology; D005260:Female; D016368:Frameshift Mutation; D006720:Homozygote; D006801:Humans; D007223:Infant; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion
chemical_list: D018389:Codon, Nonsense; D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; C032193:glycoprotein receptor GPIb-IX