Gene conversions are a common cause of von Willebrand disease
| Autor: | E. Adamtziki, A. Harbeck-Seu, Tobias Obser, Meganathan Kannan, Harsh Kumar, Renu Saxena, Ulrich Budde, M Jaiprakash, Pramod K. Gupta, Reinhard Schneppenheim, I. Wedekind, Florian Oyen |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Pediatrics medicine.medical_specialty Platelet Aggregation DNA Mutational Analysis Gene Conversion Mutation Missense India Compound heterozygosity Gastroenterology Russia Germany hemic and lymphatic diseases Internal medicine von Willebrand Factor Genotype Ethnicity Coagulopathy Von Willebrand disease Humans Medicine Missense mutation Cells Cultured Greece business.industry Haplotype Hematology medicine.disease von Willebrand Diseases Phenotype Haplotypes Ristocetin Population study business Chromosome 22 |
| Zdroj: | British Journal of Haematology. 130:752-758 |
| ISSN: | 1365-2141 0007-1048 |
| DOI: | 10.1111/j.1365-2141.2005.05660.x |
| Popis: | von Willebrand disease (VWD), the most common inherited bleeding disorder, is very heterogeneous, both in its phenotype and genotype. One particular molecular mechanism of VWD is due to recombination events between the true gene and its pseudogene on chromosome 22. We assessed the frequency and extension of such events in 50 multi-ethnic index patients with severe VWD type 3 and in five index patients with VWD type 2M Vicenza. One additional unclassified patient had been diagnosed with possible VWD in Russia solely on a clinical basis. Gene conversions, previously thought to be rare events, were identified in >10% of our study population: in six multi-ethnic patients with severe VWD type 3, in one patient with VWD type 2M Vicenza and the Russian patient was finally diagnosed with VWD type 2B New York/Malmoe. Our results suggest a significant contribution of this particular molecular mechanism to the manifestation of VWD. The location of the gene conversions, their extension and their occurrence as homozygous, compound heterozygous or heterozygous mutations determines the resulting phenotype. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text