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Bernard-Soulier syndrome Karlstad : Trp 498-->Stop mutation resulting in a truncated glycoprotein Ib alpha that contains part of the transmembranous domain

Holmberg, Lars LU ; Karpman, D LU ; Nilsson, Ingemar and Olofsson, Tor LU (1997) In British journal of haematology 98(1). p.57-63
Abstract

In Bernard-Soulier syndrome, a hereditary bleeding disorder, the platelets are deficient in the glycoprotein (GP) Ib-IX-V complex, a major receptor for the von Willebrand factor. The components of the complex are encoded by separate genes. Patients with this syndrome have a variable expression level of the receptor protein on platelets depending on the specific genetic abnormality. We describe a patient with life-long bleeding symptoms, who is homozygous for a unique stop mutation. Trp 498-->Stop in the GPIb alpha gene, resulting in a truncated GPIb alpha polypeptide chain. In contrast to previously reported truncated forms of GPIb alpha, this form contains a portion of the transmembranous domain as well as the juxtamembranous... (More)

In Bernard-Soulier syndrome, a hereditary bleeding disorder, the platelets are deficient in the glycoprotein (GP) Ib-IX-V complex, a major receptor for the von Willebrand factor. The components of the complex are encoded by separate genes. Patients with this syndrome have a variable expression level of the receptor protein on platelets depending on the specific genetic abnormality. We describe a patient with life-long bleeding symptoms, who is homozygous for a unique stop mutation. Trp 498-->Stop in the GPIb alpha gene, resulting in a truncated GPIb alpha polypeptide chain. In contrast to previously reported truncated forms of GPIb alpha, this form contains a portion of the transmembranous domain as well as the juxtamembranous cysteines engaged in a disulphide bond with GPIb beta. Flow cytometry with GPIb alpha antibodies demonstrated the presence of GPIb on the patient's platelets, although in reduced amounts compared to normal controls. GPIX was similarly detectable. Immunoblotting demonstrated that the patient synthesized a truncated GPIb alpha of the expected size of 130 K, which was, however, sensitive to proteolysis. These studies show that GPIb alpha lacking the intracytoplasmic tail can be expressed at the platelet surface provided elements of the transmembranous domain are present.

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organization
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type
Contribution to journal
publication status
published
subject
keywords
Aged, Bernard-Soulier Syndrome, Blood Platelets, Blotting, Western, Flow Cytometry, Humans, Male, Mutation, Platelet Glycoprotein GPIb-IX Complex, Sequence Analysis, DNA, Case Reports, Journal Article, Research Support, Non-U.S. Gov't
in
British journal of haematology
volume
98
issue
1
pages
7 pages
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • scopus:0030838372
ISSN
0007-1048
DOI
10.1046/j.1365-2141.1997.1772993.x
language
English
LU publication?
yes
id
3347bbae-5dc3-45d5-8af1-790d70b402a9
date added to LUP
2017-02-08 16:03:40
date last changed
2017-02-12 04:39:30
@article{3347bbae-5dc3-45d5-8af1-790d70b402a9,
  abstract     = {<p>In Bernard-Soulier syndrome, a hereditary bleeding disorder, the platelets are deficient in the glycoprotein (GP) Ib-IX-V complex, a major receptor for the von Willebrand factor. The components of the complex are encoded by separate genes. Patients with this syndrome have a variable expression level of the receptor protein on platelets depending on the specific genetic abnormality. We describe a patient with life-long bleeding symptoms, who is homozygous for a unique stop mutation. Trp 498--&gt;Stop in the GPIb alpha gene, resulting in a truncated GPIb alpha polypeptide chain. In contrast to previously reported truncated forms of GPIb alpha, this form contains a portion of the transmembranous domain as well as the juxtamembranous cysteines engaged in a disulphide bond with GPIb beta. Flow cytometry with GPIb alpha antibodies demonstrated the presence of GPIb on the patient's platelets, although in reduced amounts compared to normal controls. GPIX was similarly detectable. Immunoblotting demonstrated that the patient synthesized a truncated GPIb alpha of the expected size of 130 K, which was, however, sensitive to proteolysis. These studies show that GPIb alpha lacking the intracytoplasmic tail can be expressed at the platelet surface provided elements of the transmembranous domain are present.</p>},
  author       = {Holmberg, Lars and Karpman, D and Nilsson, Ingemar and Olofsson, Tor},
  issn         = {0007-1048},
  keyword      = {Aged,Bernard-Soulier Syndrome,Blood Platelets,Blotting, Western,Flow Cytometry,Humans,Male,Mutation,Platelet Glycoprotein GPIb-IX Complex,Sequence Analysis, DNA,Case Reports,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {1},
  pages        = {57--63},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British journal of haematology},
  title        = {Bernard-Soulier syndrome Karlstad : Trp 498-->Stop mutation resulting in a truncated glycoprotein Ib alpha that contains part of the transmembranous domain},
  url          = {http://dx.doi.org/10.1046/j.1365-2141.1997.1772993.x},
  volume       = {98},
  year         = {1997},
}