Pre-Implantation Genetic Testing for Oculocutaneous Albinism Type 1 Using Karyomapping

Abstract

Pre-Implantation Genetic Testing for Oculocutaneous Albinism Type 1 Using Karyomapping Sirivipa Piyamongkol1,† , Suchada Mongkolchaipak2,† , Winai Chaidaroon3 , Tawiwan Pantasri4 , Rungthiwa Sirapat2 , Wanwisa Suriya4 , Theera Tongsong4 , Wirawit Piyamongkol4,* 1Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, 50200 Chiang Mai, Thailand 2Suchada IVF Center, Sriracha, Chon Buri, 20110, Thailand 3Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand 4Department of Obstetrics and Gynaecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand *Correspondence: wirawit.p@cmu.ac.th (Wirawit Piyamongkol) †These authors contributed equally. Academic Editor: Shigeki Matsubara Submitted: 28 January 2022 Revised: 25 February 2022 Accepted: 28 February 2022 Published: 19 May 2022 Abstract Background: Oculocutaneous albinism type IA (OCA1) is the most severe form of albinism, an autosomal recessive inherited deficit of the pigment melanin causing distinctive alterations of skin, hair, and visual system. Pre-implantation genetic testing (PGT) is a substitution for prenatal diagnosis. Methods: This study accomplished SNP array with karyomapping for PGT of OCA1 and validated the results with PCR-based PGT. Results: One family with a risk of having OCA1 c.819+3insATATGCC and c.896G>A (p.R299H) offspring chose to go through karyomapping PGT. Novel PCR protocols employing fluorescent PCR and mini-sequencing were developed, tested, and applied. In the clinical PGT cycle, two blastocyst stage embryos were subjected to PGT. Karyotyping PGT results of OCA1 revealed both of the embryos to be normal. PCR analysis confirmed haplotyping results. However, copy number variation (CNV) analysis exhibited an additional chromosome 14 and segmental loss of 7q in embryo No. 1, i.e., 47, XY,+14,-7q, and an additional chromosome 22 in embryo No. 2, i.e., 47, XY,+22. Therefore, there was no appropriate embryo for transfer. The patient will return for the next PGT cycle. Conclusions: Karyomapping PGT for OCA1, including insertion c.819+3insATATGCC and point mutation c.896G>A (p.R299H), was performed alongside PCR techniques. Karyomapping gives benefits of CNV information to avoid the transfer of chromosomally unbalanced embryos. Keywords: oculocutaneous albinism type IA (OCA1); embryo selection; haplotyping; karyomapping; pre-implantation genetic testing for monogenic disease (PGT-M)