A phenylalanine-55 to serine amino-acid substitution in the human glycoprotein IX leucine-rich repeat is associated with Bernard-Soulier syndrome

Patrizia Noris, Suat Simsek, Jean Stibbe, Albert E G Kr Von Dem Borne

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The platelet membrane glycoprotein (GP) Ib-IX-V complex, the major von Willebrand factor receptor on platelets, is absent or dysfunctional in patients with the Bernard-Soulier syndrome (BSS). The four single subunits of the GPIb-IX-V complex (GPIbα, Ibβ, IX and V) are molecular products of different genes. Several point mutations and deletions affecting the GPIbα gene have been identified as the cause of BSS, whilst in four BSS families a GPIX gene defect has been reported. Moreover, a single case of BSS has been associated with a genetic defect of GPIbβ. We investigated the molecular basis of another case of BSS with a deficient expression of GPIX, as detected by immunofluorescence studies. After amplification of the entire GPIX coding region, nucleotide sequence analysis showed a homozygous single point mutation predicting a phenylalanine to serine substitution at position 55 of the mature GPIX within its unique leucine-rich repeat. By allele-specific oligonucleotide hybridization we confirmed the homozygosity of the patient as well as the carrier state of two out of three of his children studied. Although the parents of the patient, who were first cousins, were no longer alive and thus not available for study, we speculate that the molecular defect observed in the proband was inherited from both parents, who probably were heterozygous for this GPIX gene defect. This study confirms that BSS may be caused by many different subtle molecular defects that often prevent the assembly and expression of a functional GPIb-IX-V complex.

Original languageEnglish
Pages (from-to)312-320
Number of pages9
JournalBritish Journal of Haematology
Volume97
Issue number2
Publication statusPublished - 1997

Fingerprint

Bernard-Soulier Syndrome
Amino Acid Substitution
Phenylalanine
Leucine
Serine
Glycoproteins
Platelet Glycoprotein GPIb-IX Complex
Point Mutation
Genes
Parents
Carrier State
Oligonucleotides
Fluorescent Antibody Technique
Sequence Analysis
Blood Platelets
Alleles

Keywords

  • Bernard-Soulier syndrome
  • platelet glycoproteins

ASJC Scopus subject areas

  • Hematology

Cite this

A phenylalanine-55 to serine amino-acid substitution in the human glycoprotein IX leucine-rich repeat is associated with Bernard-Soulier syndrome. / Noris, Patrizia; Simsek, Suat; Stibbe, Jean; Von Dem Borne, Albert E G Kr.

In: British Journal of Haematology, Vol. 97, No. 2, 1997, p. 312-320.

Research output: Contribution to journalArticle

@article{9060a9af9b064f54a4f81c179498b030,
title = "A phenylalanine-55 to serine amino-acid substitution in the human glycoprotein IX leucine-rich repeat is associated with Bernard-Soulier syndrome",
abstract = "The platelet membrane glycoprotein (GP) Ib-IX-V complex, the major von Willebrand factor receptor on platelets, is absent or dysfunctional in patients with the Bernard-Soulier syndrome (BSS). The four single subunits of the GPIb-IX-V complex (GPIbα, Ibβ, IX and V) are molecular products of different genes. Several point mutations and deletions affecting the GPIbα gene have been identified as the cause of BSS, whilst in four BSS families a GPIX gene defect has been reported. Moreover, a single case of BSS has been associated with a genetic defect of GPIbβ. We investigated the molecular basis of another case of BSS with a deficient expression of GPIX, as detected by immunofluorescence studies. After amplification of the entire GPIX coding region, nucleotide sequence analysis showed a homozygous single point mutation predicting a phenylalanine to serine substitution at position 55 of the mature GPIX within its unique leucine-rich repeat. By allele-specific oligonucleotide hybridization we confirmed the homozygosity of the patient as well as the carrier state of two out of three of his children studied. Although the parents of the patient, who were first cousins, were no longer alive and thus not available for study, we speculate that the molecular defect observed in the proband was inherited from both parents, who probably were heterozygous for this GPIX gene defect. This study confirms that BSS may be caused by many different subtle molecular defects that often prevent the assembly and expression of a functional GPIb-IX-V complex.",
keywords = "Bernard-Soulier syndrome, platelet glycoproteins",
author = "Patrizia Noris and Suat Simsek and Jean Stibbe and {Von Dem Borne}, {Albert E G Kr}",
year = "1997",
language = "English",
volume = "97",
pages = "312--320",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "John Wiley & Sons, Ltd (10.1111)",
number = "2",

}

TY - JOUR

T1 - A phenylalanine-55 to serine amino-acid substitution in the human glycoprotein IX leucine-rich repeat is associated with Bernard-Soulier syndrome

AU - Noris, Patrizia

AU - Simsek, Suat

AU - Stibbe, Jean

AU - Von Dem Borne, Albert E G Kr

PY - 1997

Y1 - 1997

N2 - The platelet membrane glycoprotein (GP) Ib-IX-V complex, the major von Willebrand factor receptor on platelets, is absent or dysfunctional in patients with the Bernard-Soulier syndrome (BSS). The four single subunits of the GPIb-IX-V complex (GPIbα, Ibβ, IX and V) are molecular products of different genes. Several point mutations and deletions affecting the GPIbα gene have been identified as the cause of BSS, whilst in four BSS families a GPIX gene defect has been reported. Moreover, a single case of BSS has been associated with a genetic defect of GPIbβ. We investigated the molecular basis of another case of BSS with a deficient expression of GPIX, as detected by immunofluorescence studies. After amplification of the entire GPIX coding region, nucleotide sequence analysis showed a homozygous single point mutation predicting a phenylalanine to serine substitution at position 55 of the mature GPIX within its unique leucine-rich repeat. By allele-specific oligonucleotide hybridization we confirmed the homozygosity of the patient as well as the carrier state of two out of three of his children studied. Although the parents of the patient, who were first cousins, were no longer alive and thus not available for study, we speculate that the molecular defect observed in the proband was inherited from both parents, who probably were heterozygous for this GPIX gene defect. This study confirms that BSS may be caused by many different subtle molecular defects that often prevent the assembly and expression of a functional GPIb-IX-V complex.

AB - The platelet membrane glycoprotein (GP) Ib-IX-V complex, the major von Willebrand factor receptor on platelets, is absent or dysfunctional in patients with the Bernard-Soulier syndrome (BSS). The four single subunits of the GPIb-IX-V complex (GPIbα, Ibβ, IX and V) are molecular products of different genes. Several point mutations and deletions affecting the GPIbα gene have been identified as the cause of BSS, whilst in four BSS families a GPIX gene defect has been reported. Moreover, a single case of BSS has been associated with a genetic defect of GPIbβ. We investigated the molecular basis of another case of BSS with a deficient expression of GPIX, as detected by immunofluorescence studies. After amplification of the entire GPIX coding region, nucleotide sequence analysis showed a homozygous single point mutation predicting a phenylalanine to serine substitution at position 55 of the mature GPIX within its unique leucine-rich repeat. By allele-specific oligonucleotide hybridization we confirmed the homozygosity of the patient as well as the carrier state of two out of three of his children studied. Although the parents of the patient, who were first cousins, were no longer alive and thus not available for study, we speculate that the molecular defect observed in the proband was inherited from both parents, who probably were heterozygous for this GPIX gene defect. This study confirms that BSS may be caused by many different subtle molecular defects that often prevent the assembly and expression of a functional GPIb-IX-V complex.

KW - Bernard-Soulier syndrome

KW - platelet glycoproteins

UR - http://www.scopus.com/inward/record.url?scp=0031007623&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031007623&partnerID=8YFLogxK

M3 - Article

C2 - 9163595

AN - SCOPUS:0031007623

VL - 97

SP - 312

EP - 320

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 2

ER -