MUTATION REPORTSNovel splicing (c.6529-1G>T) and missense (c.1667G>A) mutations causing factor V deficiencyMaharaj, Satisha; Saenz Ayala, Sofiab; Hu, Xiaolinb; Chang, Simonea; Sharma, Viveka; Majerus, Juliec; Pruthi, RajivdAuthor Information aDepartment of Hematology & Oncology, University of Louisville, Louisville, Kentucky bDepartment of Medical Genetics, Cincinnati Children's Hospital, Cincinnati, Ohio cMolecular Hematopathology Laboratory, Division of Hematopathology, Department of Laboratory Medicine and Pathology dMayo Comprehensive Hemophilia Center, Special Coagulation and Molecular Hematopathology Laboratories, Mayo Clinic, Rochester, Minnesota, USA Correspondence to Satish Maharaj, MD, 529S Jackson Street, Louisville, KY 40202, USA Tel: +1 502 562 3829; fax: +1 502 562 6811; e-mail: [email protected] Received 13 July, 2020 Revised 11 November, 2020 Accepted 12 February, 2021 Blood Coagulation & Fibrinolysis: July 2021 - Volume 32 - Issue 5 - p 344-348 doi: 10.1097/MBC.0000000000001036 Buy Metrics Abstract Congenital factor V deficiency (FVD) is a rare bleeding disorder. In this study, we investigated the genetic basis in an African American patient with factor V activity 3%. Custom sequence capture and targeted next-generation (NGS) sequencing of the F5 gene were undertaken followed by PCR and Sanger sequencing. Two novel variants were identified. In silico analyses correlated clinically with the patient's factor V activity and hemorrhagic tendency. A review of the literature regarding these genomic alterations is presented. We described two novel mutations causing moderate FVD. The first, Chr1:g.169483698C>A with cDNA change (F5):c.6529-1G>T, occurred in a conserved nucleotide at the canonical acceptor splice site of intron 24. The second, Chr1:g.169515775C>T with cDNA change (F5):c.1667G>A, was a missense variant of exon 11, affecting a highly conserved amino acid in the A2 domain. Further research into the mechanisms of F5 mutations leading to FVD and residual factor V expression are needed. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.