First successful trial of preimplantation genetic diagnosis for pantothenate kinase-associated neurodegeneration.
OBJECTIVE
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.
Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama 6 Road Ratchathewi, Bangkok, 10400, Thailand. objoon.tra@mahidol.ac.th.|Center for Medical Genomics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand. objoon.tra@mahidol.ac.th.|Graduate Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand. objoon.tra@mahidol.ac.th.
Objoon
http://orcid.org/0000-0001-7867-3238
O
Trachoo
Department of Obstetrics-Gynecology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
Chonthicha
C
Satirapod
Center for Medical Genomics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.|Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
Bhakbhoom
B
Panthan
Department of Obstetrics-Gynecology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
Matchuporn
M
Sukprasert
Center for Medical Genomics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
Angkana
A
Charoenyingwattana
Center for Medical Genomics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.|Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
Wasun
W
Chantratita
Department of Obstetrics-Gynecology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
Wicharn
W
Choktanasiri
Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
Suradej
S
Hongeng
D000328:Adult; D000782:Aneuploidy; D004624:Embryo Transfer / Q000379:methods*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D006211:Pantothenate Kinase-Associated Neurodegeneration / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D011247:Pregnancy; D019836:Preimplantation Diagnosis; D020554:Sperm Injections, Intracytoplasmic
D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase
Neurodegeneration; PANK2; PGD; Pantothenate kinase; Preimplantation genetic diagnosis