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

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.

Insights in Thalassemia: From Genomics to Clinical Practice

“…After differentiation of the corrected iPSCs into erythroblasts, the gene-corrected iPSCs were successfully restored the expression of HBB compared to the parental iPSCs line. The seamless HBB correction demonstrating a critical step toward the stem cell-based gene therapy in the future (49).…”

“…This is a preferred method for individuals with medical contraindications to abortions or those who are generally against the idea of termination due to ethical or religious beliefs. It also saves the mother from physiological stress post-surgery and eliminates maternal death risk due to procedural complications (49,50). Although several existing techniques are being utilized for thalassemia PGD, there are still high error rates owing to the interruptions by allele dropouts (ADOs) and DNA contaminations (51).…”