Severe von Willebrand disease due to a defect at the level of von Willebrand factor mRNA expression: Detection by exonic PCR-restriction fragment length polymorphism analysis

Journal Article · Wed May 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.88.9.3857· OSTI ID:6056027

Nichols, W C; Lyons, S E; Harrison, J S; Cody, R L; Ginsburg, D ^[1]

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1. Univ. of Michigan, Ann Arbor (United States)

von Willebrand disease (vWD), the most common inherited bleeding disorder in humans, results from abnormalities in the plasma clotting protein von Willebrand factor (vWF). Severe (type III) vWD is autosomal recessive in inheritance and is associated with extremely low or undetectable vWF levels. The authors report a method designed to distinguish mRNA expression from the two vWF alleles by PCR analysis of peripheral blood platelet RNA using DNA sequence polymorphisms located within exons of the vWF gene. This approach was applied to a severe-vWD pedigree in which three of eight siblings are affected and the parents and additional siblings are clinically normal. Each parent was shown to carry a vWF allele that is silent at the mRNA level. Family members inheriting both abnormal alleles are affected with severe vWD, whereas individuals with only one abnormal allele are asymptomatic. Given the frequencies of the two exon polymorphisms reported here, this analysis should be applicable to {approx}70% of type I and type III vWD patients. This comparative DNA and RNA PCR-restriction fragment length polymorphism approach may also prove useful in identifying defects at the level of gene expression associated with other genetic disorders.

• OSTI ID: 6056027
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:9; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HEREDITARY DISEASES
MOLECULAR BIOLOGY
MESSENGER-RNA
TRANSCRIPTION
RFLPS
DNA SEQUENCING
BLOOD COAGULATION FACTORS
HUMAN POPULATIONS
KARYOTYPE
OLIGONUCLEOTIDES
COAGULANTS
DISEASES
DRUGS
HEMATOLOGIC AGENTS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
POPULATIONS
PROTEINS
RNA
STRUCTURAL CHEMICAL ANALYSIS
550400* - Genetics