Mutation in the gene encoding the. alpha. chain of platelet glycoprotein Ib in platelet-type von Willebrand disease

Journal Article · Sat Jun 01 00:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.11.4761· OSTI ID:6100566

Miller, J L; Cunningham, D; Lyle, V A; Finch, C N ^[1]

---

1. State Univ. of New York Health Science Center, Syracuse (United States)

Platelet-type von Willebrand disease (PT-vWD) is an autosomal dominant bleeding disorder characterized by abnormally enhanced binding of von Willebrand factor (vWF) by patient platelets. Although the platelet glycoprotein (GP) Ib/IX complex is known to constitute the platelet's ristocetin-dependent receptor for vWF, a unique structural abnormality within this complex has not previously been identified in PT-vWD. Using the poly merase chain reaction to amplify genomic DNA coding for the {alpha} chain of GP Ib (GP IB{alpha}) and then sequencing the amplified DNA following cloning into M13mp18 and M13mp19 phage vectors, the authors have found a single point mutation in the GP Ib{alpha} coding region of PT-vWD DNA resulting in the substitution of valine for glycine at residue 233. This substitution within the vWF-binding region of GP Ib{alpha} is likely to exert a significant influence on the conformation of the resulting protein. Competitive oligonucleotide primer assay for this mutation showed a homozygous wild-type pattern in genomic DNA from the 161 normal volunteers studied and from 6 phenotypically normal members of a PT-vWD family. All 7 affected members of this family studied were heterozygous for the mutant allele. Platelet GP Ib{alpha} mRNA reverse-transcribed and studied by competitive oligonucleotide primer assay showed similar expression of the mutant and wild-type alleles in the affected PT-vWD patients. Absence in the normal population, tight linkage with phenotypic expression of disease, and absence of any additional abnormality of GP Ib{alpha} in these patients identify the glycine-to-valine substitution as a point mutation underlying functional abnormality of the vWF receptor in PT-vWD.

• OSTI ID: 6100566
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:11; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GLYCOPROTEINS
GENE MUTATIONS
HEREDITARY DISEASES
ETIOLOGY
BLOOD PLATELETS
DNA POLYMERASES
DOMINANT MUTATIONS
GENE AMPLIFICATION
OLIGONUCLEOTIDES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
DISEASES
ENZYMES
MATERIALS
MUTATIONS
NUCLEIC ACIDS
NUCLEOTIDYLTRANSFERASES
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
PROTEINS
TRANSFERASES
550201* - Biochemistry- Tracer Techniques