title: Bernard-soulier syndrome with a homozygous 13 base pair deletion in the signal peptide-coding region of the platelet glycoprotein Ib(beta) gene.
abstract: We report a family with Bernard-Soulier syndrome with a homozygous mutation within the GPIb(beta) gene. The proband was a 24-year-old Japanese male who has suffered from life-long bleeding tendency. The patient's sister also had severe bleeding episodes. The proband and the affected sister had no apparent complications including organic or skeletal anomaly, or mental disturbance. They had thrombocytopenia [(35-40) x 10(9)/l] with giant platelets. In addition to platelet size, electron microscopic analysis revealed abnormalities in the internal structures of platelets. Ristocetin-induced platelet aggregation was defective. Flow cytometric analysis and western blot analysis showed that glycoprotein IX was nearly absent in platelets, whereas GPIb(alpha) and GPV were detectable. Genetic studies revealed a 13 base pair deletion in the signal peptide-coding sequence of GPIb(beta). The deletion would cause a frame-shift, resulting in the appearance of a stop codon following an indifferent polypeptide sequence. Analysis of platelet RNA showed that the mutant GPIb(beta) gene was transcribed. The propositus and his affected sister were homozygous for the deletion, whereas their unaffected father and mother were heterozygotes. The molecular defects of this family would help understand the relevance of GPIb(beta) for complex formation of the glycoprotein Ib/IX/V receptor.
authors.affiliation: Department of Hematology, Keio University, Tokyo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Watanabe
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Yurie
authors.initials: Y
authors.lastname: Saitoh
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shichishima
authors.forename: Yukio
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Enomoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Handa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Oda
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ambo
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Murata
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001606:Bernard-Soulier Syndrome / Q000097:blood / Q000150:complications / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D003062:Codon / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005434:Flow Cytometry; D006470:Hemorrhage / Q000150:complications / Q000235:genetics; D006720:Homozygote; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010375:Pedigree; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D021382:Protein Sorting Signals / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
chemical_list: D003062:Codon; D019038:Platelet Glycoprotein GPIb-IX Complex; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D004247:DNA