Abstract
Hemophilia B (HB) is a coagulation disorder with an X-linked recessive inheritance pattern, caused by plasma FIX deficiency. In Colombia, HB is considered a rare and high-cost disease, with 362 males reported in 2017. Here, we characterized 20 HB apparently unrelated families by PCR amplification and Sanger sequencing. Fourteen unique variants were identified: seven missense, three nonsense, one variant in the 3' UTR region, two large deletions >50 bp, and one intronic substitution that affects splicing c.520+13A>G that was present in 7/20 patients (35%). All these variants have been previously reported in the literature, except for exons 3 and 4, deletions, present in one patient. The genotype-phenotype association correlates with the reported in the literature, with the exception of one patient. This molecular analysis allowed us to establish the causal variant of HB in 100% of patients, to provide the appropriate genetic counseling to each of the families, and to propose a more cost-effective carrier analysis. Here, we reported the first variants in Colombian population with Hemophilia B, finding a new variant and one intron recurrent variant present in 35% of patients.
References
Aug 1, 1993·Human Molecular Genetics·E VielhaberS S Sommer
Oct 1, 1997·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·M G ReeseD Haussler
Aug 31, 2002·Nucleic Acids Research·Vasily RamenskyShamil Sunyaev
Aug 10, 2006·Bioinformatics·E CapriottiR Casadio
Aug 11, 2010·Haemophilia : the Official Journal of the World Federation of Hemophilia·A AwidiA S Fauori
Jul 11, 2012·Haemophilia : the Official Journal of the World Federation of Hemophilia·A SrivastavaUNKNOWN Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia
Oct 25, 2012·Thrombosis and Haemostasis·Claudia Pamela RadicCarlos Daniel De Brasi
Apr 27, 2013·Journal of Thrombosis and Haemostasis : JTH·P M RallapalliS J Perkins
Jan 1, 2014·American Journal of Hematology·Tengguo LiW Craig Hooper
Feb 6, 2014·Molecular Genetics & Genomic Medicine·Tengguo LiW Craig Hooper
Apr 1, 2014·Nature Methods·Jana Marie SchwarzDominik Seelow
Apr 9, 2015·Journal of Thrombosis and Haemostasis : JTH·A C Goodeve
Nov 28, 2015·Haemophilia : the Official Journal of the World Federation of Hemophilia·A MårtenssonR Ljung
Mar 5, 2016·Human Mutation·Johan T den DunnenPeter E M Taschner
May 20, 2016·Bioinformatics·Haiming Tang, Paul D Thomas
Jun 18, 2016·Advances in Bioinformatics·Rongying TangDonald R Love
Jul 20, 2017·Haemophilia : the Official Journal of the World Federation of Hemophilia·M R MeirelesE Bandinelli
Jul 29, 2017·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Muhammad Tariq Masood KhanAbid Sohail Taj