Preimplantation Genetic Diagnosis of Neurodegenerative Diseases: Review of Methodologies and Report of Our Experience as a Regional Reference Laboratory
Chun-Hua Liao,
Ming-Yuh Chang,
Gwo-Chin Ma,
Shun-Ping Chang,
Chi-Fang Lin,
Wen-Hsiang Lin,
Hsin-Fu Chen,
Shee-Uan Chen,
Yi-Chung Lee,
Chi-Chao Chao,
Ming Chen,
Sung-Tsang Hsieh
Affiliations
Chun-Hua Liao
Department of Pediatrics, National Taiwan University Children’s Hospital, Taipei 10041, Taiwan
Ming-Yuh Chang
Division of Pediatric Neurology, Department of Pediatrics, Changhua Christian Children’s Hospital, Changhua 50050, Taiwan
Gwo-Chin Ma
Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan
Shun-Ping Chang
Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan
Chi-Fang Lin
Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei 10041, Taiwan
Wen-Hsiang Lin
Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan
Hsin-Fu Chen
Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei 10041, Taiwan
Shee-Uan Chen
Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei 10041, Taiwan
Yi-Chung Lee
Department of Neurology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
Chi-Chao Chao
Department of Neurology, National Taiwan University Hospital, Taipei 10048, Taiwan
Ming Chen
Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan
Sung-Tsang Hsieh
Department of Neurology, National Taiwan University Hospital, Taipei 10048, Taiwan
Preimplantation genetic diagnosis (PGD) has become a crucial approach in helping carriers of inherited disorders to give birth to healthy offspring. In this study, we review PGD methodologies and explore the use of amplification refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR) and/or linkage analysis for PGD in neurodegenerative diseases that are clinically relevant with typical features, such as late onset, and which are severely debilitating. A total of 13 oocyte retrieval cycles were conducted in 10 cases with various neurodegenerative diseases. Among the 59 embryos analyzed, 49.2% (29/59) were unaffected and 50.8% (30/59) were affected. Of the 12 embryo transfer cycles, three resulted in pregnancy, and all pregnancies were delivered. The implantation rate and livebirth rate were 23.1% (3/13) per oocyte retrieval cycle and 25.0% (3/12) per embryo transfer cycle. Allele dropout (ADO) was noted in two embryos that were classified as unaffected by ARMS-qPCR but were evidenced as affected after prenatal diagnosis, rendering the false negative rate as 6.3% (2/32). Four among the 13 cycles underwent PGD by ARMS-qPCR coupled with linkage analysis, and all were correctly diagnosed. We conclude that PGD by ARMS-qPCR and/or linkage analysis is a feasible strategy, whereas ADO is a concern when ARMS-qPCR is used as the sole technology in PGD, especially in autosomal dominant diseases.
