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Search for mutations in a segment of the exon 28 of the human von Willebrand factor gene: New mutations, R1315C and R1341W, associated with type 2M and 2B variants

1998; Wiley; Volume: 59; Issue: 1 Linguagem: Inglês

10.1002/(sici)1096-8652(199809)59

1096-8652

Pilar Casaña, Francisco Martı́nez, Carmen Espinós, Saturnino Haya, José Ignacio Lorenzo, José A. Aznar,

Hemophilia Treatment and Research

American Journal of HematologyVolume 59, Issue 1 p. 57-63 Free Access Search for mutations in a segment of the exon 28 of the human von Willebrand factor gene: New mutations, R1315C and R1341W, associated with type 2M and 2B variants Pilar Casaña, Corresponding Author Pilar Casaña [email protected] Unidad de Coagulopatías Congénitas de la Comunidad Valenciana, Hospital La Fe, Valencia, SpainUnidad de Coagulopatías Congénitas, Hospital La Fe, Avda. Campanar, 21, 46009 Valencia, SpainSearch for more papers by this authorFrancisco Martínez, Francisco Martínez Unidad de Genética y Diagnóstico Prenatal, Hospital La Fe, Valencia, SpainSearch for more papers by this authorCarmen Espinós, Carmen Espinós Unidad de Coagulopatías Congénitas de la Comunidad Valenciana, Hospital La Fe, Valencia, SpainSearch for more papers by this authorSaturnino Haya, Saturnino Haya Unidad de Coagulopatías Congénitas de la Comunidad Valenciana, Hospital La Fe, Valencia, SpainSearch for more papers by this authorJosé I. Lorenzo, José I. Lorenzo Unidad de Coagulopatías Congénitas de la Comunidad Valenciana, Hospital La Fe, Valencia, SpainSearch for more papers by this authorJosé A. Aznar, José A. Aznar Unidad de Coagulopatías Congénitas de la Comunidad Valenciana, Hospital La Fe, Valencia, SpainSearch for more papers by this author Pilar Casaña, Corresponding Author Pilar Casaña [email protected] Unidad de Coagulopatías Congénitas de la Comunidad Valenciana, Hospital La Fe, Valencia, SpainUnidad de Coagulopatías Congénitas, Hospital La Fe, Avda. Campanar, 21, 46009 Valencia, SpainSearch for more papers by this authorFrancisco Martínez, Francisco Martínez Unidad de Genética y Diagnóstico Prenatal, Hospital La Fe, Valencia, SpainSearch for more papers by this authorCarmen Espinós, Carmen Espinós Unidad de Coagulopatías Congénitas de la Comunidad Valenciana, Hospital La Fe, Valencia, SpainSearch for more papers by this authorSaturnino Haya, Saturnino Haya Unidad de Coagulopatías Congénitas de la Comunidad Valenciana, Hospital La Fe, Valencia, SpainSearch for more papers by this authorJosé I. Lorenzo, José I. Lorenzo Unidad de Coagulopatías Congénitas de la Comunidad Valenciana, Hospital La Fe, Valencia, SpainSearch for more papers by this authorJosé A. Aznar, José A. Aznar Unidad de Coagulopatías Congénitas de la Comunidad Valenciana, Hospital La Fe, Valencia, SpainSearch for more papers by this author First published: 07 December 1998 https://doi.org/10.1002/(SICI)1096-8652(199809)59:1 3.0.CO;2-ZCitations: 25AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract von Willebrand Disease (vWD) is the most frequently inherited bleeding disorder in humans, and is caused by a qualitative and/or quantitative abnormality of the von Willebrand factor (vWF). A large number of defects that cause qualitative variants have been located in the A1 domain of the vWF, which contains sites for interaction with platelet glycoprotein Ib (GPIb). We have developed a new approach to detect mutations based on Dde digestion and single-strand conformation polymorphism analysis. A segment of 487 nucleotides, extending from intron 27 to codon 1368 of the pre-pro vWF was amplified from genomic DNA. The cleavage with Dde yields two fragments of appropriate size for this kind of analysis and confirms that the gene, rather than the pseudogene, is being investigated. Six families with type 2B vWD, one type 2M vWD family, and one another type 2A vWD family were studied. After sequencing the fragments with an altered electrophoretic pattern, we found four mutations previously described—R1308C, V1316M, P1337L, and R1306W—in patients with 2B vWD. The last one arose de novo in the patient. In addition, two new candidate mutations were observed: R1315C and R1341W. The first one was associated to type 2M vWD, whereas the one second cosegregated with type 2B vWD. The fact that these new mutations were not found in 100 normal alleles screened further supports their causal relationship with the disease. These mutations, which induce either a gain or a loss of function, further show an important regulatory role of this region in the binding of vWF to GPIb and its implications in causing disease. Am. J. Hematol. 59:57–63, 1998. © 1998 Wiley-Liss, Inc. References 1 Ruggeri ZM, Zimmerman TS: von Willebrand factor and von Willebrand disease. 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Biochem Biophys Res Commun 182: 561– 568, 1992. 25 Bird AP: DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res 8: 1499– 1504, 1980. Citing Literature Volume59, Issue1September 1998Pages 57-63 ReferencesRelatedInformation