title: A point mutation in glycoprotein IX coding sequence (Cys73 (TGT) to Tyr(TAT)) causes impaired surface expression of GPIb/IX/V complex in two families with Bernard-Soulier syndrome.
abstract: Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder which is caused by abnormal expression or function of the glycoprotein (GP) Ib/IX/V complex, a platelet major receptor for von Willebrand factor. We studied four BSS patients in two unrelated families in which the same and novel mutation was found. Flow cytometric analysis showed that GPIX was completely absent but residual amounts of GPIb alpha and GPV were detectable in these patients. We analyzed all coding regions of GPIb alpha, GPIb beta, GPV and GPIX which were amplified from the patients' genomic DNA by the polymerase chain reaction (PCR). In all four cases, we identified a point mutation in the GPIX coding region that changes the codon for cysteine 73 (TGT) to a codon for tyrosine (TAT). Furthermore, we confirmed by a transient expression study that the mutation caused the loss of adequate surface expression of GPIX. Since cysteine might be important for the secondary structure, this mutation of GPIX gene would lead to a dramatic conformational change of GPIX protein, resulting in the reduced surface expression. We concluded that this novel point mutation of the GPIX gene was responsible for BSS in these families.
authors.affiliation: Department of Hematology and Oncology, Hiroshima University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Noda
authors.forename: K
authors.initials: K
authors.lastname: Fujimura
authors.forename: T
authors.initials: T
authors.lastname: Takafuta
authors.forename: T
authors.initials: T
authors.lastname: Shimomura
authors.forename: T
authors.initials: T
authors.lastname: Fujii
authors.forename: S
authors.initials: S
authors.lastname: Katsutani
authors.forename: T
authors.initials: T
authors.lastname: Fujimoto
authors.forename: A
authors.initials: A
authors.lastname: Kuramoto
authors.forename: T
authors.initials: T
authors.lastname: Yamazaki
authors.forename: T
authors.initials: T
authors.lastname: Mochizuki
authors.forename: M
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: M
authors.initials: M
authors.lastname: Sano
mesh_terms: D000328:Adult; D001606:Bernard-Soulier Syndrome / Q000097:blood / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism*; D003545:Cysteine / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D017354:Point Mutation; D014443:Tyrosine / Q000235:genetics
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; D014443:Tyrosine; D003545:Cysteine