Molecular Basis of Human Von Willebrand Disease: Analysis of Platelet Von Willebrand Factor mRNA

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-05, Vol.86 (10), p.3723-3727
• Main Authors: Ginsburg, David, Konkle, Barbara A., Gill, Joan Cox, Montgomery, Robert R., Bockenstedt, Paula L., Johnson, Timothy A., Yang, Angela Y.
• Format: Article
• Language: English
• Subjects: 550401 - Genetics- Tracer Techniques; Alleles; AMINO ACIDS; Base Sequence; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; Biological and medical sciences; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BLOOD COAGULATION FACTORS; Blood plasma; BLOOD PLATELETS; BODY FLUIDS; CARBOXYLIC ACIDS; COAGULANTS; CYSTEINE; DAYS LIVING RADIOISOTOPES; DISEASES; DNA; DNA POLYMERASES; DNA SEQUENCING; DRUGS; ELECTROPHORESIS; ENZYMES; EVEN-ODD NUCLEI; Fundamental and applied biological sciences. Psychology; Gene Amplification; Genes; Genes. Genome; Genetic mutation; Genomics; GLYCOPROTEINS; HEMATOLOGIC AGENTS; HEREDITARY DISEASES; Humans; ISOTOPES; LIGHT NUCLEI; LIPOTROPIC FACTORS; MATERIALS; MESSENGER-RNA; METHIONINE; Molecular and cellular biology; MOLECULAR BIOLOGY; Molecular genetics; Mutation; NUCLEI; NUCLEIC ACIDS; NUCLEOTIDYLTRANSFERASES; Oligonucleotide Probes; OLIGONUCLEOTIDES; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; Pedigree; PHOSPHORUS-GROUP TRANSFERASES; Platelets; Polymerase chain reaction; POLYMERASES; PROTEINS; RADIOISOTOPES; RNA; RNA POLYMERASES; RNA, Messenger - genetics; STRUCTURAL CHEMICAL ANALYSIS; SULFUR 35; SULFUR ISOTOPES; THIOLS; TRANSCRIPTION; TRANSFERASES; von Willebrand Diseases - genetics; von Willebrand Factor - genetics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.10.3723

Von Willebrand disease (vWD), the most common inherited bleeding disorder in humans, can result from either a quantitative or a qualitative defect in the adhesive glycoprotein, von Willebrand factor (vWF). Molecular studies of vWD have been limited by the large size of the vWF gene and difficulty in obtaining the vWF mRNA from patients. By use of an adaptation of the polymerase chain reaction, vWF mRNA was amplified and sequenced from peripheral blood platelets. A silent vWF allele was identified, resulting from a cis defect in vWF mRNA transcription or processing. In two type IIA vWD patients, two different but adjacent missense mutations were identified, the locations of which may identify an important vWF functional domain. Expression in heterologous cells of recombinant vWF containing one of these latter mutations reproduced the characteristic structural abnormality seen in type IIA vWD plasma.