Abstract
Purpose
We aim to present a case of a healthy infant born after intracytoplasmic sperm injection-in vitro fertilization (ICSI-IVF) with a preimplantation genetic diagnosis (PGD) for pantothenate kinase-associated neurodegeneration (PKAN) due to PANK2 mutation.
Methods
ICSI-IVF was performed on a Thai couple, 34-year-old female and 33-year-old male, with a family history of PKAN in their first child. Following fertilization, each of the embryos were biopsied in the cleavage stage and subsequently processed for whole-genome amplification. Genetic status of the embryos was diagnosed by linkage analysis and direct mutation testing using primer extension-based mini-sequencing. Comprehensive chromosomal aneuploidy screening was performed using a next-generation sequencing-based strategy.
Results
Only a single cycle of ICSI-IVF was processed. There were seven embryos from this couple—two were likely affected, three were likely carriers, one was likely unaffected, and one failed in target genome amplification. Aneuploidy screening was performed before making a decision on embryo transfer, and only one unaffected embryo passed the screening. That embryo was transferred in a frozen thawed cycle, and the pregnancy was successful. The diagnosis was confirmed by amniocentesis, which presented with a result consistent with PGD. At 38 weeks of gestational age, a healthy male baby was born. Postnatal genetic confirmation was also consistent with PGD and the prenatal results. At the age of 24 months, the baby presented with normal growth and development lacking any neurological symptoms.
Conclusions
We report the first successful trial of PGD for PKAN in a developing country using linkage analysis and mini-sequencing in cleavage stage embryos.
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Acknowledgments
This work is a part of the project entitled “Stem cell-based technology as research models for genetic disorders; diagnostic strategies, treatment discovery and disease prevention” (S. Hongeng as the principal investigator). The research was supported in grants to the sub-project “Search the molecular basis of rare genetic disorders as a model for disease prevention using preimplantation blastocyst technology” (to O. Trachoo) and “Preimplantation genetic diagnosis for rare genetic disorders” (to W. Choktanasiri) by Mahidol University and the National Research Council of Thailand. The grants for next-generation sequencing were partially supported by the Center for Medical Genomics in collaboration between the Faculty of Medicine, Ramathibodi Hospital, Mahidol University, and the Thailand Center of Excellence for Life Science (TCELS), Ministry of Science, Thailand (to W. Chantratita). We are grateful to the couple for their excellent participation in the project; to Dr. K. Sakpichaisakul, Maharat Nakhon Ratchasima Hospital, Thailand, for nice clinical data collection and referral; to B. Matthayomchan and P. Srikittayakorn, Thai Reproductive Genetic Laboratory for technical assistance in embryo biopsy; to the people in the Center for Medical Genomics and Stem Cell Research Cluster, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Thailand, for their kind comments during project progression; and to Professor P. Sritara, Dean of Faculty of Medicine Ramathibodi Hospital, for support and encouragement.
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Pantothenate kinase-associated neurodegeneration is a life-threatening and incurable autosomal recessive disorder characterized by progressive extrapyramidal dysfunction. Here we present the first successful trial to utilize preimplantation genetic diagnosis technology for a couple who had an experience on the loss of their first child affected by this particular inherited neurological condition.
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Trachoo, O., Satirapod, C., Panthan, B. et al. First successful trial of preimplantation genetic diagnosis for pantothenate kinase-associated neurodegeneration. J Assist Reprod Genet 34, 109–116 (2017). https://doi.org/10.1007/s10815-016-0833-y
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DOI: https://doi.org/10.1007/s10815-016-0833-y