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* '''Preimplantation genetic diagnosis as a strategy to prevent having a child born with an heritable eye disease'''{{#pmid:29781739|PMID29781739}} "In developed countries, genetically inherited eye diseases are responsible for a high percentage of childhood visual impairment. We aim to report our experience using preimplantation genetic diagnostics (PGD) in order to avoid transmitting a genetic form of eye disease associated with childhood visual impairment and ocular cancer. MATERIAL AND METHODS: Retrospective case series of women who underwent in vitro fertilization (IVF) and PGD due to a familial history of inherited eye disease and/or ocular cancer, in order to avoid having a child affected with the known familial disease. Each family underwent genetic testing in order to identify the underlying disease-causing mutation. IVF and PGD treatment were performed; unaffected embryos were implanted in their respective mothers. RESULTS: Thirty-five unrelated mothers underwent PGD, and the following hereditary conditions were identified in their families: albinism (10 families); retinitis pigmentosa (7 families); retinoblastoma (4 families); blue cone monochromatism, achromatopsia, and aniridia (2 families each); and Hermansky-Pudlak syndrome, Leber congenital amaurosis, Norrie disease, papillorenal syndrome, primary congenital cataract, congenital glaucoma, Usher syndrome type 1F, and microphthalmia with coloboma (1 family each). Following a total of 88 PGD cycles, 18 healthy (i.e., unaffected) children were born." {{vision}} | |||
* '''The first successful application of preimplantation genetic diagnosis for hearing loss in Iran'''{{#pmid:30030956|PMID30030956}} "Hearing impairment (HI) caused by mutations in the connexin-26 gene (GJB2) accounts for the majority of cases with inherited, nonsyndromic sensorineural hearing loss. Due to the illegality of the abortion of deaf fetuses in Islamic countries, preimplantation genetic diagnosis (PGD) is a possible solution for afflicted families to have a healthy offspring. This study describes the first use of PGD for GJB2 associated non-syndromic deafness in Iran. GJB2 donor splicing site IVS1+1G>A mutation analysis was performed using Sanger sequencing for a total of 71 Iranian families with at least 1 deaf child diagnosed with non-syndromic deafness. In Vitro Fertilization (IVF) was performed, followed by PGD for a cousin couple with a 50% chance of having an affected child. Bi-allelic pathogenic mutations were found in a total of 12 families (~17 %); of which a couple was a PGD volunteer. The deaf woman in this family was homozygous and her husband was a carrier of the IVS1+1G>A gene mutation. Among 8 biopsied embryos, two healthy embryos were implanted which resulted in a single pregnancy and subsequent birth of a healthy baby boy. This is the first report of a successful application of PGD for hearing loss in Iran." {{hearing}} | |||
* '''Review - Genetic Analysis of Human Preimplantation Embryos'''{{#pmid:27475859|PMID27475859}} "Preimplantation development comprises the initial stages of mammalian development, before the embryo implants into the mother's uterus. In normal conditions, after fertilization the embryo grows until reaching blastocyst stage. The blastocyst grows as the cells divide and the cavity expands, until it arrives at the uterus, where it "hatches" from the zona pellucida to implant into the uterine wall. Nevertheless, embryo quality and viability can be affected by chromosomal abnormalities, most of which occur during gametogenesis and early embryo development; human embryos produced in vitro are especially vulnerable. Therefore, the selection of chromosomally normal embryos for transfer in assisted reproduction can improve outcomes in poor-prognosis patients. Additionally, in couples with an inherited disorder, early diagnosis could prevent pregnancy with an affected child and would, thereby, avoid the therapeutic interruption of pregnancy. These concerns have prompted advancements in the use of preimplantation genetic diagnosis (PGD). Genetic testing is applied in two different scenarios: in couples with an inherited genetic disorder or carriers of a structural chromosomal abnormality, it is termed PGD; in infertile couples with increased risk of generating embryos with de novo chromosome abnormalities, it is termed preimplantation genetic screening, or PGS." | * '''Review - Genetic Analysis of Human Preimplantation Embryos'''{{#pmid:27475859|PMID27475859}} "Preimplantation development comprises the initial stages of mammalian development, before the embryo implants into the mother's uterus. In normal conditions, after fertilization the embryo grows until reaching blastocyst stage. The blastocyst grows as the cells divide and the cavity expands, until it arrives at the uterus, where it "hatches" from the zona pellucida to implant into the uterine wall. Nevertheless, embryo quality and viability can be affected by chromosomal abnormalities, most of which occur during gametogenesis and early embryo development; human embryos produced in vitro are especially vulnerable. Therefore, the selection of chromosomally normal embryos for transfer in assisted reproduction can improve outcomes in poor-prognosis patients. Additionally, in couples with an inherited disorder, early diagnosis could prevent pregnancy with an affected child and would, thereby, avoid the therapeutic interruption of pregnancy. These concerns have prompted advancements in the use of preimplantation genetic diagnosis (PGD). Genetic testing is applied in two different scenarios: in couples with an inherited genetic disorder or carriers of a structural chromosomal abnormality, it is termed PGD; in infertile couples with increased risk of generating embryos with de novo chromosome abnormalities, it is termed preimplantation genetic screening, or PGS." | ||
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Revision as of 10:27, 23 July 2018
Embryology - 19 Apr 2024 Expand to Translate |
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Introduction
This current page is a general starting point for the topic of Preimplantation Genetic Screening also called Preimplantation Genetic Diagnosis (PGD) began during the 1990's as an alternative to prenatal diagnosis.
Recently with the growth in Assisted Reproductive Technology (ART) or commonly known as In Vitro Fertilization (IVF), there is now a new form of prenatal diagnosis that involves genetic testing of the blastocyst before implantation. (More? Assisted Reproductive Technology)
Generally, in vitro fertilised embryos are first cultured for up to three days. By this time the conceptus is composed of 6 to 10 cells (blastomeres) from which 1 or 2 cells are then removed by a laser for genetic testing. Some studies have also removed cells, or the polar body, at earlier days following fertilisation. While other studies have collected cells from later stage (day 5) blastocyst either the trophectoderm (trophoblast) or inner cell mass (embryoblast).
- This Embryology site is a developmental educational resource, it does not provide specific clinical details, you should always refer to a health professional.
| Assisted Reproductive Technology | In Vitro Fertilization
Some Recent Findings
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More recent papers |
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This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Preimplantation Genetic Diagnosis <pubmed limit=5>Preimplantation Genetic Diagnosis</pubmed> |
Older papers |
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Genetic Testing
Trisomy
There are clinically more and more tests becoming available as we learn more about the genetic basis of some diseases. The most common diagnostic test relates to the current trend in an increasing maternal age, which has long been associated with an increase in genetic abnormalities, the most frequent of these is trisomy 21 or Down syndrome.
- Links: Genetic risk maternal age | Trisomy 21
Single Gene Disorders
- Cystic fibrosis
- beta-thalassaemia
- Spinal muscular atrophy
- Sickle-cell anaemia
- Huntington disease
- Myotonic dystrophy type 1
- Duchenne or Becker muscular dystrophy
- Haemophilia
- Fragile-X syndrome
Australia
A recent publication from NHMRC Medical Genetic Testing: information for health professionals (2010). This paper covers background information on all types of genetic tests, not just those associated with prenatal diagnosis.
Types of genetic tests
- Somatic cell genetic testing involves testing tissue (usually cancer) for non-heritable mutations. This may be for diagnostic purposes, or to assist in selecting treatment for a known cancer.
- Diagnostic testing for heritable mutations involves testing an affected person to identify the underlying mutation(s) responsible for the disease. This typically involves testing one or more genes for a heritable mutation.
- Predictive testing for heritable mutations involves testing an unaffected person for a germline mutation identified in genetic relatives. The risk of disease will vary according to the gene, the mutation and the family history.
- Carrier testing for heritable mutations involves testing for the presence of a mutation that does not place the person at increased risk of developing the disease, but does increase the risk of having an affected child developing the disease.
- Pharmacogenetic testing for a genetic variant that alters the way a drug is metabolised. These variants can involve somatic cells or germline changes. Even if these variants are heritable (that is germline changes), the tests are usually of relevance to genetic relatives only if they are being treated with the same type of medication.
USA
A new site developed by NIH "GeneTests" provides medical genetics information resources available at no cost to all interested persons. It contains educational information, a directory of genetic testing laboratories and links to other databases such as OMIM.
- Links: GeneTests | Medline Plus - Genetic Testing
Ethics of Testing
Major developmental abnormalities detected early enough can be resolved far more easily than those discovered late in a pregnancy.
What are the ethical questions that are raised by prenatal testing? Future individual rights or parents rights? But what about diseases, like Huntington's, where a diagnostic test can be made but there are no current treatments for the postnatal (95% of cases adult onset) disease?
Huntington's disease
Guidelines for the molecular genetics predictive test
- Recommendation 2.1 "the test is available only to individuals who have reached the age of majority."
- Recommendation 7.2 "the couple requesting antenatal testing must be clearly informed that if they intend to complete the pregnancy if the fetus is a carrier of the gene defect, there is no valid reason for performing the test."
References
- ↑ Yahalom C, Macarov M, Lazer-Derbeko G, Altarescu G, Imbar T, Hyman JH, Eldar-Geva T & Blumenfeld A. (2018). Preimplantation genetic diagnosis as a strategy to prevent having a child born with an heritable eye disease. Ophthalmic Genet. , 39, 450-456. PMID: 29781739 DOI.
- ↑ Karimi Yazdi A, Davoudi-Dehaghani E, Rabbani Anari M, Fouladi P, Ebrahimi E, Sabeghi S, Eftekharian A, Fatemi KS, Emami H, Sharifi Z, Ramezanzadeh F, Tajdini A, Zeinali S & Amanpour S. (2018). The first successful application of preimplantation genetic diagnosis for hearing loss in Iran. Cell. Mol. Biol. (Noisy-le-grand) , 64, 1718. PMID: 30030956
- ↑ Garcia-Herrero S, Cervero A, Mateu E, Mir P, Póo ME, Rodrigo L, Vera M & Rubio C. (2016). Genetic Analysis of Human Preimplantation Embryos. Curr. Top. Dev. Biol. , 120, 421-47. PMID: 27475859 DOI.
- ↑ Gleicher N, Kushnir VA & Barad DH. (2014). Preimplantation genetic screening (PGS) still in search of a clinical application: a systematic review. Reprod. Biol. Endocrinol. , 12, 22. PMID: 24628895 DOI.
- ↑ Rabinowitz M, Ryan A, Gemelos G, Hill M, Baner J, Cinnioglu C, Banjevic M, Potter D, Petrov DA & Demko Z. (2012). Origins and rates of aneuploidy in human blastomeres. Fertil. Steril. , 97, 395-401. PMID: 22195772 DOI.
- ↑ Ramón Y Cajal T, Polo A, Martínez O, Giménez C, Arjona C, Llort G, Bassas L, Viscasillas P & Calaf J. (2012). Preimplantation genetic diagnosis for inherited breast cancer: first clinical application and live birth in Spain. Fam. Cancer , 11, 175-9. PMID: 22179695 DOI.
- ↑ Van Rij MC, De Rademaeker M, Moutou C, Dreesen JC, De Rycke M, Liebaers I, Geraedts JP, De Die-Smulders CE & Viville S. (2012). Preimplantation genetic diagnosis (PGD) for Huntington's disease: the experience of three European centres. Eur. J. Hum. Genet. , 20, 368-75. PMID: 22071896 DOI.
Reviews
<pubmed>22216843</pubmed> <pubmed>21743973</pubmed>
Articles
<pubmed>21397558</pubmed> <pubmed>20966462</pubmed> <pubmed>20966461</pubmed> <pubmed>20966460</pubmed> <pubmed>20966459</pubmed>
Journals
Search PubMed
Search Pubmed: Preimplantation Genetic Screening | Preimplantation Genetic Diagnosis
- ART - Assisted Reproductive Technology a general term to describe all the clinical techniques used to aid fertility.
- blastomere biopsy - An ART preimplantation genetic diagnosis technique carried out at cleavage stage (day 3), excluding poor quality embryos, detects chromosomal abnormalities of both maternal and paternal origin. May not detect cellular mosaicism in the embryo.
- blastocyst biopsy - An ART preimplantation genetic diagnosis technique carried out at blastocyst stage (day 4-5), removes several trophoblast (trophoderm) cells, detects chromosomal abnormalities of both maternal and paternal origin and may detect cellular mosaicism.
- cell-free fetal deoxyribonucleic acid - (cfDNA) refers to fetal DNA circulating and isolated from the plasma portion of maternal blood. Can be performed from GA 10 weeks as a first-tier test or as a second-tier test, with women with increased probability on combined first trimester screening offered cfDNA or diagnostic testing.
- false negative rate - The proportion of pregnancies that will test negative given that the congenital anomaly is present.
- false positive rate - The proportion of pregnancies that will test positive given that the congenital anomaly is absent.
- free β human chorionic gonadotrophin - beta-hCG subunit of hCG used as a diagnostic marker for: early detection of pregnancy, Trisomy 21, spontaneous abortion, ectopic pregnancy, hydatidiform mole or choriocarcinoma.
- multiples of the median - (MoM) A multiple of the median is a measure of how far an individual test result deviates from the median and is used to report the results of medical screening tests, particularly where the results of the individual tests are highly variable.
- negative predictive value - The probability that a congenital anomaly is absent given that the prenatal screening test is negative.
- Non-Invasive Prenatal Testing - (NIPT) could refer to ultrasound or other imaging techniques, but more frequently used to describe analysis of cell-free fetal DNA circulating in maternal blood.
- polar body biopsy - (PB biopsy) An ART preimplantation genetic diagnosis technique that removes either the first or second polar body from the zygote. As these are generated by oocyte meiosis they detects chromosomal abnormalities only on the female genetics.
- positive predictive value - The probability that a congenital anomaly is present given that the prenatal screening test is positive.
- pre-implantation genetic diagnosis - (PGD, pre-implantation genetic screening) a diagnostic procedure for embryos produced through Assisted Reproductive Technology (ART, in vitro fertilisation, IVF) for genetic diseases that would generate developmental abnormalities or serious postnatal diseases.
- prenatal screening sensitivity - (detection rate) The probability of testing positive on a prenatal screening test if the congenital anomaly is present.
- prenatal screening specificity - The probability of testing negative on a prenatal screening test if the congenital anomaly is absent.
- quadruple test (maternal serum testing of a-fetoprotein Template:AFP, free B-hCG or total hCG, unconjugated estriol, and inhibin A) is a fetal chromosomal anomaly test usually carried out later in pregnancy (GA 14 to 20 weeks).
- single nucleotide polymorphisms - (SNPs) the variation in a single DNA nucleotide that occurs at a specific position in the genome.
- triple test - (maternal serum testing of a-fetoprotein Template:AFP, free B-hCG or total hCG, and unconjugated estriol) is a fetal chromosomal anomaly test usually carried out later in pregnancy (GA 14 to 20 weeks).
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Cite this page: Hill, M.A. (2024, April 19) Embryology Preimplantation Genetic Diagnosis. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Preimplantation_Genetic_Diagnosis
- © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G