文献_-2012-Blastocyst preimplantation genetic diagnosis (PGD) of a mitochondrial DNA disorder.pdfVIP

ORIGINAL ARTICLES: GENETICS Blastocyst preimplantation genetic diagnosis (PGD) of a mitochondrial DNA disorder Nathan R. Treff, Ph.D.,a,b,c Jessyca Campos, M.S.,a,b Xin Tao, M.S.,a Brynn Levy, Ph.D.,d Kathleen M. Ferry, B.S.,a and Richard T. Scott Jr., M.D.a,b a Reproductive Medicine Associates of New Jersey, Morristown; b Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology, and Reproductive Science, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick; c Department of Genetics, Rutgers University, Piscataway, New Jersey; and d Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York Objective: To evaluate the utility of trophectoderm biopsy for preimplantation genetic diagnosis (PGD) of mitochondrial (mt) DNA mutation load. Design: A PGD case and analysis of blastocyst mosaicism. Setting: Academic center for reproductive medicine. Patient(s): A 30-year-old carrier of 35% 3243A G mtDNA mutation load with a daughter affected by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Intervention(s): Blastocyst biopsy for PGD of mutation load and gender. Main Outcome Measure(s): Variation in mutation load within and among embryos, and newborn mutation load after PGD-based selection. Result(s): Oocytes and embryos were found to possess a variety of 3243AG mutation loads from 9% to 90% in oocytes and 7% to 91% in embryos, demonstrating that PGD would be a relevant procedure. Highly consistent results were obtained within multiple biopsies of both cleavage- and blastocyst-stage embryos. Importantly, mutation loads observed in trophectoderm were predictive of the inner cell mass (r2 ¼ 0.97). Transfer of a male embryo, predicted to possess 12% mutation load by analysis of a trophectoderm biopsy, resulted in the deliv