%0 Journal Article
%T Targeted Next-Generation Resequencing of Gene Identifies Novel Multiple Variants Pattern in Severe Hereditary Factor V Deficiency
%A Piotr K. Janicki
%A Sonia Vaida
%A Hamid A. B. AL-Mondhiry
%J Case Reports in Genetics
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/941684
%X The present study investigated the genetic defects underlying severe Factor V deficiency in a 26-year-old Columbian (South America) female and her immediate family (both parents and newborn child) by next generation sequencing (NGS) of the entire gene locus. Five mutations in the coding sequence of , including three missense single-nucleotide variants (R2102H, R513K, D107H) and two synonymous variants (A135A , S184S), were identified and confirmed by the Sanger sequencing in the investigated proband (homozygote for all detected mutations), her parents, and her newborn child (all heterozygotic carriers for identified mutations). Each of the three missense variants was previously associated with separate phenotypes, including Factor V deficiency (R2102H), thrombosis (R513K) and frequent miscarriages (D107H). In addition, at least 75 additional single-nucleotide variants (including six novels) were identified in untranslated region of . 1. Introduction Coagulation Factor V is a large 330-kD glycoprotein which consists of 2224 amino acid residues including a 28-residue leader peptide, which is structurally and functionally homologous to coagulation Factor VIII [1, 2]. The human Factor V gene (official name ) maps to chromosome 1q23 and contains 25 exons (8). Factor V deficiency is a rare autosomal recessive disorder (incidence < 1 in 1 million), characterized by low levels of antigen and activity [3]. At present, more than one hundred deficiency-causing mutations in the locus have been described, and although most of them are private, a few are common, being found in several individuals of both European, Middle-Eastern and Asiatic descents. In the present study, we used for the first time DNA next-generation sequence (NGS) analysis to detect mutation pattern in the entire locus of a 26-year-old Hispanic parturient with severe Factor V deficiency, as well as in her asymptomatic parents and newborn baby. The relationship between combinations of mutations and clinical phenotypes was evaluated. 2. Case Presentation The study protocol was approved by IRB at PSU Hershey Medical College. It was performed in adherence to the tenets of the declaration of Helsinki. Written informed consent was obtained from all participants. The investigated patient was 26-year-old Hispanic (born in Columbia, South America) parturient (G4P1) with several bleeding episodes before and during present pregnancy, multiple fresh frozen plasma (FFP) transfusions, and a history of three miscarriages in the past. The patient was previously diagnosed clinically to have severe Factor V
%U http://www.hindawi.com/journals/crig/2013/941684/