An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease
| Autor: | Charles R. M. Hay, Frank Hill, Andrea Guilliatt, Peter William Collins, Pamela Grundy, William Lester, Derrick John Bowen, A. M. Cumming, Stephen Keeney, Said Enayat, John Pasi, Paula H B Bolton-Maggs, David Keeling |
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| Rok vydání: | 2006 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities Genotype Genetic Linkage DNA Mutational Analysis Penetrance Biology Gene mutation medicine.disease_cause Von Willebrand factor Polymorphism (computer science) hemic and lymphatic diseases von Willebrand Factor Von Willebrand disease medicine Humans Family Health Genetics Mutation Polymorphism Genetic Haplotype Hematology medicine.disease United Kingdom Pedigree von Willebrand Diseases Haplotypes Immunology biology.protein Female |
| Zdroj: | Thrombosis and Haemostasis. 96:630-641 |
| ISSN: | 2567-689X 0340-6245 |
| Popis: | SummaryForty families diagnosed by UK centres to have type 1 VWD were recruited. Following review, six families were re-diagnosed to have type 2 VWD, one to have a platelet storage pool disorder, and one family was determined to be unaffected. Direct DNA sequencing of the promoter region and all exons and intronic boundaries of the VWF gene identified six mutations likely to be causative of VWD in index cases of nine of the 32 (28%) confirmed type 1 VWD families. These included R1205H (3614G>A) VWD Vicenza, P1648fsX45 (4944delT), D141G (422A>G) and three splice site mutations: 3108+5G>A, 7437+1G>A and 3379+1G>A. The Y1584C (4751A>G) polymorphism was present in eight additional families. No significant VWF gene mutation or polymorphism was identified in 15 of the32 type 1VWD index cases (47%). Haplotype studies were performed using a panel of VWF polymorphisms to investigate the segregation in families of VWD phenotype with the VWF gene. In 13 of the 32 families it was likely that VWD segregated with the VWF gene. In eight families (25%) VWD clearly did not segregate with the VWF gene. We suggest that mutation screening of the VWF gene has limited general utility in genetic diagnostic and family studies in type 1 VWD. If genetic studies are performed, the incomplete penetrance and variable expressivity of type 1 VWD must be taken into account. Unless linkage of VWD phenotype with the VWF gene can be clearly demonstrated, the results of any genetic family studies should be interpreted with caution. |
| Databáze: | OpenAIRE |
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