In-frame deletion of von Willebrand factor A domains in a dominant type of von Willebrand disease
| Autor: | G. Ballerini, Giovanna Marchetti, Donato Gemmati, P. Patracchini, C. Schwienbacher, Mirko Pinotti, Francesco Bernardi |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Molecular Sequence Data Alu element medicine.disease_cause Polymerase Chain Reaction Von Willebrand factor hemic and lymphatic diseases von Willebrand Factor Genetics medicine Von Willebrand disease Humans VWF Missense mutation RNA Messenger Molecular Biology Gene Genetics (clinical) Genes Dominant Repetitive Sequences Nucleic Acid Sequence Deletion Mutation dominant-negative effects Base Sequence biology multimeric protein gene deletion Intron Chromosome Mapping DNA General Medicine medicine.disease Molecular biology von Willebrand Diseases Biosynthetic process biology.protein |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/2.5.545 |
| Popis: | von Willebrand disease (vWD), the most common inherited bleeding disorder in humans, is very heterogeneous and has been classified into several subtypes. Missense mutations have been found to be responsible for the dominant type II vWD, characterized by qualitative abnormalities affecting von Willebrand factor (vWF) function. The breakpoints of a heterozygous vWF gene deletion (31 Kb), occurring 'de novo' in a patient with a variant of type II vWD, were localized to introns 25 and 34 and sequenced. An Alu repeat in intron 25 was interrupted between the transcriptional boxes A and B. The new junction present in the abnormal von Willebrand factor mRNA was sequenced after reverse transcription of platelet RNA. The codon 1104 (Cys) is followed in frame by the mutated codon 1926 (Cys to Arg), thus removing the complete A domains, found in a wide variety of genes and characterized by independent assembly 'in vitro'. We propose that the abnormal vWF, which carries intact protein domains responsible for vWF dimer and multimer formation, makes ineffective interactions with the normal molecules in the biosynthetic process, causing the dominant type II phenotype through a novel mechanism. |
| Databáze: | OpenAIRE |
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