title: Preimplantation genetic diagnosis of hemophilia A.
abstract: Preimplantation genetic diagnosis (PGD) is a powerful tool to tackle the transmission of monogenic inherited disorders in families carrying the diseases from generation to generation. It currently remains a challenging task, despite PGD having been developed over 25 years ago. The major difficulty is it does not have an easy and general formula for all mutations. Different gene locus needs individualized, customized design to make the diagnosis accurate enough to be applied on PGD, in which the quantity of DNA is scanty, whereas timely laboratory diagnosis is mandatory if fresh embryo transfer is desired occasionally. Indicators for outcome assessment of a successful PGD program include the successful diagnosis rate on blastomeres (Day 3 cleavage-stage embryo biopsy) or trophectoderm cells (Day 5/6 blastocyst biopsy), the implantation rate per embryo transferred, and the livebirth rate per oocyte retrieval cycle. Hemophilia A (HA) is an X-linked recessive bleeding disorder caused by various types of pathological defects in the factor VIII gene (F8). The mutation spectrum of theF8is complex, according to our previous report, including large segmental intra-gene inversions, large segmental deletions spanning a few exons, point mutations, and total deletion caused by chromosomal structural rearrangements. In this review, the molecular methodologies used to tackle different mutants of theF8in the PGD of HA are to be explained, and the experiences of successful use of amplification refractory mutation system-quantitative polymerase chain reaction (ARMS-qPCR) and linkage analysis for PGD of HA in our laboratory are also provided.
authors.affiliation: Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan.|Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua, Taiwan.|Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan.|Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.|Department of Life Science, Tunghai University, Taichung, Taiwan.|Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan.|Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua, Taiwan.
authors.forename: Shun-Ping
authors.initials: SP
authors.lastname: Chang
authors.affiliation: Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan.|Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua, Taiwan.|Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.|Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: Gwo-Chin
authors.initials: GC
authors.lastname: Ma
authors.affiliation: Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan.|Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua, Taiwan.
authors.forename: Wen-Hsian
authors.initials: WH
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsin-Fu
authors.initials: HF
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Shee-Uan
authors.initials: SU
authors.lastname: Chen
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Horng-Der
authors.initials: HD
authors.lastname: Tsai
authors.affiliation: Po-Yuan Women's Clinic and IVF Center, Changhua, Taiwan.
authors.forename: Feng-Po
authors.initials: FP
authors.lastname: Tsai
authors.affiliation: Department of Internal Medicine, and Thrombosis and Hemostasis Center, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Shen
keywords: ARMS-qPCR; Linkage analysis; PGD; Polymorphism; STR marker