Germ-line mosaicism for a valine-to-methionine substitution at residue 553 in the glycoprotein Ib-binding domain of von Willebrand factor, causing type IIB von Willebrand disease

Journal Article · Wed Jan 01 00:00:00 EST 1992 · American Journal of Human Genetics; (United States)

OSTI ID:5378979

Murray, E W; Giles, A R; Lillicrap, D ^[1]

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1. Queen's Univ., Kingston, Ontario (Canada)

The origin of new single-gene mutations resulting in inherited disease is an issue which may be at least partially resolved by our enhanced ability to detect these changes. In this report the authors describe the identification of a missense mutation at codon 553 (guanine to adenine) in the von Willebrand factor (vWf) gene in affected members of a family with type IIB von Willebrand's disease (vWd). They found no evidence for this substitution in 190 normal vWf genes. The encoded substitution of a methionine for a valine at this residue is nonconservative in nature and has affected a vWf protein region which has been shown to facilitate binding to the platelet receptor glycoprotein Ib. In patients with type IIb vWd this interaction is characteristically increased in affinity. This mutation has also recently been recorded in four other type IIb vWd families. Thus, there is strong circumstantial evidence to incriminate this substitution as the disease causing mutation in this family. As further supporting evidence for this claim, they have shown by vWf polymorphism analysis that the mutation originated in a vWf gene transmitted from a phenotypically normal grandfather. These results confirm (1) that the candidate type IIB vWd mutation in this family occurred at some time during the development of the germ line of the grandfather and presumably was related to a mitotic cell division and (2) that, as a result, he is a low-level germ-line mosaic for the mutation.

• OSTI ID: 5378979
• Journal Information: American Journal of Human Genetics; (United States), Vol. 50:1; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GENE MUTATIONS
MOLECULAR BIOLOGY
HEREDITARY DISEASES
ETIOLOGY
BLOOD PLATELETS
DNA SEQUENCING
GLYCOPROTEINS
METHIONINE
PATIENTS
RFLPS
VALINE
AMINO ACIDS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
DISEASES
DRUGS
LIPOTROPIC FACTORS
MATERIALS
MUTATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
550200* - Biochemistry