ORIGINAL ARTICLESA novel splicing mutation in F8 causes various aberrant transcripts in a hemophilia A patient and identifies a new transcript from healthy individualsYi, Shenga,∗; Zuo, Yangjina,∗; Yu, Qiuxiab; Yang, Qia; Li, Mengtinga; Lan, Yueyuna; Huang, Limeia; Zhang, Qinlea; Qin, Zailonga; Luo, JingsiaAuthor Information aLaboratory of Genetics and Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning bDepartment of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou, People's Republic of China Correspondence to Jingsi Luo, Laboratory of Genetics and Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, People's Republic of China E-mail: [email protected] Received 1 April, 2020 Revised 19 July, 2020 Accepted 4 August, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.bloodcoagulation.com). Blood Coagulation & Fibrinolysis: December 2020 - Volume 31 - Issue 8 - p 506-510 doi: 10.1097/MBC.0000000000000952 Buy SDC Metrics Abstract Hemophilia A is an X-linked hemorrhagic disorder caused by deficiency or dysfunction of the coagulation factor VIII (FVIII), and a great variety of mutations in the factor VIII gene (F8) are identified. We aimed to identify the genetic defects of the F8 gene in a Chinese patient with moderate hemophilia A. We have identified a novel intronic variant in the hemophilia A patient by DNA sequence analysis, cDNA sequencing, and TA clone sequencing. An intronic variant, c.5816-1G>A, was identified and the cDNA sequencing confirmed the pathogenicity of the transition. TA clone sequencing showed that the splicing mutation produced two aberrant premRNA skipping exons (18 and exon 18 + 19, respectively). These aberrant mRNA forms maintain the reading frame and are predicted to code for deleted FVIII isoforms and the shorter abnormal transcript accounted for one-eighth of the total mRNA. There was a new unreported transcript with E22 spliced out in healthy individuals and our patient, whose specific functions need to be determined in further studies. Our study widens the mutation spectrum of the F8 gene. In addition, the study findings could provide the opportunity to reveal alternative splicing patterns. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.