Preimplantation genetic diagnosis in mitochondrial DNA disorders: challenge and success

Sallevelt, Suzanne C E H; Dreesen, Joseph C F M; Drüsedau, Marion; Spierts, Sabine; Coonen, Edith; Tienen, F.H.J. van; Golde, Ronald J T van; Coo, I.F.M. de; Geraedts, J. P. M.; Die-Smulders, C.E.M. de; Smeets, Hubert J.M.

doi:10.1136/jmedgenet-2012-101172

Cited by 82 publications

(75 citation statements)

References 55 publications

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“…For this technique to be reliable, the mtDNA mutation level in the biopsied blastomere must be representative of the mutation level in the remaining embryo, assuming that the mutant mtDNA segregates uniformly across all blastomeres during early embryo cleavage. Limited studies in human embryos have revealed that this is often the case, and although exceptions have been reported (76,95), there are generally low levels of variation in heteroplasmy among blastomeres of cleavage-stage embryos (67,76,93). Alternatively, the biopsy can be performed at the blastocyst stage of development, which involves removing a small number of trophectoderm cells.…”

Section: Preimplantation Genetic Diagnosismentioning

confidence: 99%

“…This technique involves genetic testing of cells removed from early embryos obtained during in vitro fertilization procedures and allows the selection of embryos with a reduced risk of mitochondrial disease for implantation. Although experience is still limited, preimplantation genetic diagnosis has been used for a small number of different mtDNA mutations and has successfully identified suitable embryos for transfer with undetectable or low levels of mtDNA mutation (39,67,76,84,93). For the majority of preimplantation genetic diagnosis cases, the biopsy has been performed on cleavage-stage embryos at the eight-cell stage of development, which involves removing one or two blastomeres for testing.…”

Section: Preimplantation Genetic Diagnosismentioning

confidence: 99%

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Recent Advances in Mitochondrial Disease

Craven

Alston

Taylor

et al. 2017

Annu. Rev. Genom. Hum. Genet.

243

198

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Mitochondrial disease is a challenging area of genetics because two distinct genomes can contribute to disease pathogenesis. It is also challenging clinically because of the myriad of different symptoms and, until recently, a lack of a genetic diagnosis in many patients. The last five years has brought remarkable progress in this area. We provide a brief overview of mitochondrial origin, function, and biology, which are key to understanding the genetic basis of mitochondrial disease. However, the primary purpose of this review is to describe the recent advances related to the diagnosis, genetic basis, and prevention of mitochondrial disease, highlighting the newly described disease genes and the evolving methodologies aimed at preventing mitochondrial DNA disease transmission.

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Section: Preimplantation Genetic Diagnosismentioning

confidence: 99%

Section: Preimplantation Genetic Diagnosismentioning

confidence: 99%

Recent Advances in Mitochondrial Disease

Craven

Alston

Taylor

et al. 2017

Annu. Rev. Genom. Hum. Genet.

243

198

View full text Add to dashboard Cite

show abstract

“…The problem with this option is that PGD involves extracting a cell from an embryo that has passed the one-cell stage, and then testing it. 39 Resorting to PGD necessarily implies that we would be unable to afterwards use MSTpg or PNT, because MSTpg takes place before fertilization and PNT takes place at the one-cell stage. Therefore, PGD would not serve as an adequate tool to indicate the moral permissibility of carrying out MSTpg or PNT.…”

Section: Mitochondrial Replacement Techniques: a Habermasian Perspectivementioning

confidence: 99%

“…We must conclude, at this point, that, from a Habermasian perspective, it would only be morally permissible to use PNT or MSTpg when we know, accurately and in advance, that an extreme evil would be prevented by such techniques. 40 A second theoretical shortcoming of Habermass position is manifest when dealing with genetic conditions that appear within a spectrum that ranges from mild to devastating. It seems that Habermas is oblivious to the fact that most genetic conditions manifest in varying degrees due to other intrinsic and extrinsic factors.…”

Section: Mitochondrial Replacement Techniques: a Habermasian Perspectivementioning

confidence: 99%

Ethics of Mitochondrial Replacement Techniques: A Habermasian Perspective

Palacios-González¹

2016

Bioethics

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J€ urgen Habermas is regarded as a central bioconservative commentator in the debate on the ethics of human prenatal genetic manipulations. While his main work on this topic, The Future of Human Nature, has been widely examined in regard to his position on prenatal genetic enhancement, his arguments regarding prenatal genetic therapeutic interventions have for the most part been overlooked. In this work I do two things. First, I present the three necessary conditions that Habermas establishes for a prenatal genetic manipulation to be regarded as morally permissible. Second, I examine if mitochondrial replacement techniques meet these necessary conditions. I investigate, specifically, the moral permissibility of employing pronuclear transfer and maternal spindle transfer. I conclude that, according to a Habermasian perspective on prenatal genetic manipulation, maternal spindle transfer (without using a preselected sperm and egg) and pronuclear transfer are morally impermissible. Maternal spindle transfer is, in principle, morally permissible, but only when we have beforehand preselected a sperm and an egg for our reproductive purpose. These findings are relevant for bioconservatives, both for those who hold a Habermasian stance and for those who hold something akin to a Habermasian stance, because they answer the question: what should bioconservatives do regarding mitochondrial replacement techniques? In fact, the answer to this question does not only normatively prescribe what bioconservatives should do in terms of their personal morality, but it also points towards what kind of legislation regulating mitochondrial replacement techniques they should aim at.

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“…Así, es empleado en casos de talasemia (5) , de enfermedad de Huntington (6) , portadores de translocaciones robertsonianas (7) , mujeres portadoras de enfermedades mitocondriales (encefalopatía mitocondrial, acidosis láctica, episodios parecidos a apoplejía) (8) y en el futuro se prevé su uso para descartar el autismo (9) . Su utilidad ha quedado demostrada al disminuir en 25 a 81% el número de embriones disponibles para transferir, lo que permite disminuir los embarazos múltiples al hacer posible la transferencia de un solo embrión, así como la criopreservación de blastocistos.…”

Section: Dr José Pacheco Romero Jpachecoperu@yahoocomunclassified

Editorial

Romero¹

2013

An Fac med

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La coca (Erythroxylum coca) es un arbusto sudamericano que se halla en las estribaciones de los Andes amazónicos. Desde épocas remotas, ha sido utilizada en el Perú como estimulante (1) . Se dice que la primera descripción del empleo de la cocaína se encuentra en las memorias del viajero florentino Américo Vespucci (1451-1512) y que los primeros estudios experimentales en animales fueron realizados por el cirujano peruano Moréno y Maïz (2) . En 1880, Basil von Anrep (1852Anrep ( -1925 se refirió a la aplicación de la cocaína en humanos, recomendando su empleo en la anestesia quirúrgica. William Stewart Halsted (1852-1922 y Richard John Hall (1856-1897) desarrollaron técnicas de bloqueo nervioso y regional (3) . Además, la coca ha sido empleada en la analgesia y en el mal de altura (4) , una infusión de la cual nos espera a los costeños a nuestro arribo a la sierra. Presentamos el artículo Efecto terapéutico del extracto etanólico de Erythroxylum coca spp. en anemia ferropénica inducida en ratas Holtzman macho, en donde se le haya a la coca una nueva propiedad a nivel experimental, en la anemia ferropénica inducida por dieta deficiente en hierro, lo cual es sustentado por la variación de los niveles de hemoglobina.El diagnóstico genético preimplantación (PGD, por sus siglas en inglés) se realiza en los procedimientos de reproducción asistida en parejas con infertilidad, con el fin de transferir solo los embriones 'normales' y evitar aquellos con fallas genéticas o cromosómicas. Así, es empleado en casos de talasemia (5) , de enfermedad de Huntington (6) , portadores de translocaciones robertsonianas (7) , mujeres portadoras de enfermedades mitocondriales (encefalopatía mitocondrial, acidosis láctica, episodios parecidos a apoplejía) (8) y en el futuro se prevé su uso para descartar el autismo (9) . Su utilidad ha quedado demostrada al disminuir en 25 a 81% el número de embriones disponibles para transferir, lo que permite disminuir los embarazos múltiples al hacer posible la transferencia de un solo embrión, así como la criopreservación de blastocistos. Su empleo es aún controversial, entre otros, por las consideraciones éticas (10) y porque añade una 'cuarta dimensión' -el aspecto emocional-al tratamiento con tecnología de reproducción asistida (11) .El artículo Diagnóstico genético preimplantacional: análi-sis de aneuploidías únicas, presenta la experiencia con esta técnica en la detección de aneuploidías únicas en embriones de buena calidad en el día 3 de desarrollo hasta llegar a blastocisto. El 63% de 355 embriones estudiados que presentaron monosomías únicas al tercer día de desarrollo embrionario tenía 8 células. Pero, al día cinco, 42,3% resultó anormal, y de estos 37,5% perteneció al estadio de 8 células. Esto lleva a concluir a los autores que los embriones de 8 células en el tercer día de desarrollo embrionario tienen más probabilidad de llegar al estadio de blastocisto, así como de presentar aneuploidías únicas; la buena calidad morfológica no asegura una normalidad cromosómica.Los siguientes tres ar...

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Preimplantation genetic diagnosis in mitochondrial DNA disorders: challenge and success

Abstract: PGD provides carriers of mtDNA mutations the opportunity to conceive healthy offspring.

Cited by 82 publications

References 55 publications

Recent Advances in Mitochondrial Disease

Recent Advances in Mitochondrial Disease

Ethics of Mitochondrial Replacement Techniques: A Habermasian Perspective

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