Abstract
Hereditary factor XI deficiency is a rare bleeding disorder with worldwide distribution. In Austrian patients only one mutation leading to congenital factor XI deficiency has been reported. In the present study, we identified the molecular basis of factor XI deficiency in three Austrian patients. Patients attended hospital for other reasons than bleeding disorders. Routine laboratory tests revealed prolonged APTTs due to decreased factor XI levels. We performed automated fluorescent sequencing of the promotor region, exons 1-15 and the flanking intronic regions of the factor XI gene. The mutations found were confirmed by restriction enzyme analysis or sequencing of the non-coding strand. Fluorescent sequencing revealed two novel mutations, the nonsense mutation Gln116X (443C>T) in exon 5 and a deletion of Ile197 and Asp198 (687_692delTCGACA) in exon 7. Furthermore, we detected a heterozygous A>G exchange at the third nucleotide of IVS6 (IVS 6 +3A>G), which had already been reported in a FXI deficient individual of French Basque origin. While the IVS 6 +3A>G decreases the calculated splice consensus score from 0.98 in the wild type to 0.56 in the altered sequence and therefore interferes with the consensus splice sequence, the c...Continue Reading
References
Feb 26, 1991·Biochemistry·B A McMullenE W Davie
Jul 18, 1991·The New England Journal of Medicine·R AsakaiU Seligsohn
Nov 17, 1987·Biochemistry·R AsakaiD W Chung
Aug 1, 1995·British Journal of Haematology·Y ImanakaJ H McVey
Dec 24, 1997·British Journal of Haematology·B WistinghausenM Karpatkin
Feb 23, 1999·British Journal of Haematology·A AlhaqG Savidge
Dec 22, 1999·British Journal of Haematology·M MitchellA Alhaq
Mar 8, 2000·American Journal of Hematology·E SatoK Oshimi
Dec 21, 2000·British Journal of Haematology·K IijimaS Ikawa
Jul 14, 2001·Fitoterapia·V U AhmadM Nisar
Sep 21, 2001·British Journal of Haematology·A Dossenbach-GlaningerP Hopmeier
Mar 16, 2002·Blood·Ariella ZivelinUri Seligsohn
Apr 29, 2003·British Journal of Haematology·Michael MitchellAnwar Alhaq
Jul 25, 2003·American Journal of Hematology·Akiko TsukaharaTetsuhito Kojima
Sep 26, 2003·American Journal of Hematology·W Y AuY L Kwong
Jan 14, 2004·Journal of Thrombosis and Haemostasis : JTH·F QuélinE Fressinaud
Mar 18, 2004·Blood·Dmitri V KravtsovDavid Gailani
Apr 3, 2004·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Philippe de MoerlooseMarguerite Neerman-Arbez
Jun 8, 2004·British Journal of Haematology·Letian DaiAnwar Alhaq
Oct 1, 2004·Journal of Thrombosis and Haemostasis : JTH·A ZivelinD Gailani
Apr 22, 2005·Journal of Thrombosis and Haemostasis : JTH·G JayandharanA Srivastava