scholarly journals ESHRE PGT Consortium good practice recommendations for the organisation of PGT†

2020 ◽  
Vol 2020 (3) ◽  
Author(s):  
Filipa Carvalho ◽  
Edith Coonen ◽  
Veerle Goossens ◽  
Georgia Kokkali ◽  
Carmen Rubio ◽  
...  
Keyword(s):  
Best Practice ◽  
Single Gene ◽  
Good Practice ◽  
Diagnostic Testing ◽  
Genetic Diagnosis ◽  
Information Provision ◽  
Embryo Biopsy ◽  
Preimplantation Genetic Testing ◽  
Gene Defects

Abstract The field of preimplantation genetic testing (PGT) is evolving fast, and best practice advice is essential for regulation and standardisation of diagnostic testing. The previous ESHRE guidelines on best practice for preimplantation genetic diagnosis, published in 2005 and 2011, are considered outdated and the development of new papers outlining recommendations for good practice in PGT was necessary. The current updated version of the recommendations for good practice is, similar to the 2011 version, split into four documents, one of which covers the organisation of a PGT centre. The other documents focus on the different technical aspects of embryo biopsy, PGT for monogenic/single-gene defects (PGT-M) and PGT for chromosomal structural rearrangements/aneuploidies (PGT-SR/PGT-A). The current document outlines the steps prior to starting a PGT cycle, with details on patient inclusion and exclusion, and counselling and information provision. Also, recommendations are provided on the follow-up of PGT pregnancies and babies. Finally, some further recommendations are made on the practical organisation of an IVF/PGT centre, including basic requirements, transport PGT and quality management. This document, together with the documents on embryo biopsy, PGT-M and PGT-SR/PGT-A, should assist everyone interested in PGT in developing the best laboratory and clinical practice possible.

scholarly journals ESHRE PGT Consortium and SIG Embryology good practice recommendations for polar body and embryo biopsy for PGT†

2020 ◽  
Vol 2020 (3) ◽  
Author(s):  
Georgia Kokkali ◽  
Giovanni Coticchio ◽  
Fernando Bronet ◽  
Catherine Celebi ◽  
Danilo Cimadomo ◽  
...  
Keyword(s):  
Best Practice ◽  
Single Gene ◽  
Polar Body ◽  
Good Practice ◽  
Diagnostic Testing ◽  
Embryo Biopsy ◽  
Preimplantation Genetic Testing ◽  
Technical Aspects ◽  
Practice Recommendations ◽  
Blastocyst Biopsy

Abstract The field of preimplantation genetic testing (PGT) is evolving fast, and best practice advice is essential for regulation and standardisation of diagnostic testing. The previous ESHRE guidelines on best practice for PGD, published in 2005 and 2011, are considered outdated, and the development of new papers outlining recommendations for good practice in PGT was necessary. The current paper provides recommendations on the technical aspects of embryo biopsy and covers recommendations on the biopsy procedure, cryopreservation and laboratory issues and training, in addition to technical aspects and strengths and limitations specific for currently used techniques at different stages (polar body, cleavage stage and blastocyst biopsy). Furthermore, alternative sampling methods are briefly described.This paper is one of a series of four papers on good practice recommendations on PGT. The other papers cover the organisation of PGT, and the different technical aspects of PGT for monogenic/single-gene defects (PGT-M) and PGT for chromosomal structural rearrangements/aneuploidies (PGT-SR/PGT-A). Together, these papers should assist everyone interested in PGT in developing the best laboratory and clinical practice possible.

scholarly journals ESHRE PGT Consortium good practice recommendations for the detection of monogenic disorders†

2020 ◽  
Vol 2020 (3) ◽  
Author(s):  
Filipa Carvalho ◽  
Céline Moutou ◽  
Eftychia Dimitriadou ◽  
Jos Dreesen ◽  
Carles Giménez ◽  
...  
Keyword(s):  
Best Practice ◽  
De Novo ◽  
Single Gene ◽  
Good Practice ◽  
Hla Typing ◽  
Preimplantation Genetic Testing ◽  
Technical Aspects ◽  
Practice Recommendations ◽  
Pathogenic Variants ◽  
Special Cases

Abstract The field of preimplantation genetic testing (PGT) is evolving fast and best practice advice is essential for regulation and standardisation of diagnostic testing. The previous ESHRE guidelines on best practice for PGD, published in 2005 and 2011, are considered outdated, and the development of new papers outlining recommendations for good practice in PGT was necessary. The current paper provides recommendations on the technical aspects of PGT for monogenic/single-gene defects (PGT-M) and covers recommendations on basic methods for PGT-M and testing strategies. Furthermore, some specific recommendations are formulated for special cases, including de novo pathogenic variants, consanguineous couples, HLA typing, exclusion testing and disorders caused by pathogenic variants in the mitochondrial DNA. This paper is one of a series of four papers on good practice recommendations on PGT. The other papers cover the organisation of a PGT centre, embryo biopsy and tubing and the technical aspects of PGT for chromosomal structural rearrangements/aneuploidies. Together, these papers should assist scientists interested in PGT in developing the best laboratory and clinical practice possible.

scholarly journals Contributions of Rare Gene Variants to Familial and Sporadic FSGS

2019 ◽  
Vol 30 (9) ◽  
pp. 1625-1640 ◽  
Author(s):  
Minxian Wang ◽  
Justin Chun ◽  
Giulio Genovese ◽  
Andrea U. Knob ◽  
Ava Benjamin ◽  
...  
Keyword(s):  
Rare Variants ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Unrelated Family ◽  
The Past ◽  
New Genes ◽  
Rare Gene ◽  
Gene Defects ◽  
Disease Associated Genes ◽  
Burden Tests

BackgroundOver the past two decades, the importance of genetic factors in the development of FSGS has become increasingly clear. However, despite many known monogenic causes of FSGS, single gene defects explain only 30% of cases.MethodsTo investigate mutations underlying FSGS, we sequenced 662 whole exomes from individuals with sporadic or familial FSGS. After quality control, we analyzed the exome data from 363 unrelated family units with sporadic or familial FSGS and compared this to data from 363 ancestry-matched controls. We used rare variant burden tests to evaluate known disease-associated genes and potential new genes.ResultsWe validated several FSGS-associated genes that show a marked enrichment of deleterious rare variants among the cases. However, for some genes previously reported as FSGS related, we identified rare variants at similar or higher frequencies in controls. After excluding such genes, 122 of 363 cases (33.6%) had rare variants in known disease-associated genes, but 30 of 363 controls (8.3%) also harbored rare variants that would be classified as “causal” if detected in cases; applying American College of Medical Genetics filtering guidelines (to reduce the rate of false-positive claims that a variant is disease related) yielded rates of 24.2% in cases and 5.5% in controls. Highly ranked new genes include SCAF1, SETD2, and LY9. Network analysis showed that top-ranked new genes were located closer than a random set of genes to known FSGS genes.ConclusionsAlthough our analysis validated many known FSGS-causing genes, we detected a nontrivial number of purported “disease-causing” variants in controls, implying that filtering is inadequate to allow clinical diagnosis and decision making. Genetic diagnosis in patients with FSGS is complicated by the nontrivial rate of variants in known FSGS genes among people without kidney disease.

scholarly journals Can expelled cells/debris from a developing embryo be used for PGT?

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Adva Aizer ◽  
Noa Harel-Inbar ◽  
Hagit Shani ◽  
Raoul Orvieto
Keyword(s):  
Zona Pellucida ◽  
Single Gene ◽  
Molecular Genetic ◽  
Embryo Biopsy ◽  
Human Embryos ◽  
Cell Debris ◽  
Preimplantation Genetic Testing ◽  
Blastomere Biopsy ◽  
Wide Range ◽  
Genetic Results

Abstract Background Preimplantation genetic testing (PGT) is offered to a wide range of structural and numerical chromosomal imbalances, with PGT- polymerase chain reaction (PCR), as the method of choice for amplifying the small DNA content achieved from the blastomere biopsy or trophectoderm (TE) biopsy, that might have a detrimental impact on embryonic implantation potential. Since human embryos cultured until Day-5–6 were noticed to expel cell debris/ fragments within the zona pellucida, we aimed to examine whether these cell debris/ fragments might be used for PGT, as an alternative to embryo biopsy. Methods Blastocysts, which their Day-3 blastomere biopsy revealed an affected embryo with single-gene defect, and following hatching leaved cell debris/fragments within the zona pellucida were analyzed. Each blastocyst and its corresponding cell debris/fragments were separated and underwent the same molecular analysis, based on multiplex PCR programs designed for haplotyping using informative microsatellites markers. The main outcome measure was the intra-embryo congruity of Day-3 blastomere biopsy and its corresponding blastocyst and cell debris/fragments. Results Fourteen affected embryos from 9 women were included. Only 8/14 (57.2%) of embryos demonstrated congruent molecular genetic results between Day-3 embryo and its corresponding blastocyst and cell debris/fragments. In additional 6/14 (42.8%) embryos, molecular results of the Day-3 embryos and their corresponding blastocysts were congruent, while the cell debris/fragments yielded no molecular diagnoses (incomplete diagnoses). Conclusions It might be therefore concluded, that in PGT cycles, examining the cell debris/fragments on Day-4, instead of Day-3 blastomere or Day-5 TE biopsies, is feasible and might avoid embryo biopsy with its consequent detrimental effect on embryos’ implantation potential. Whenever the latter results in incomplete diagnosis, TE biopsy should be carried out on Day-5 for final genetic results. Further large well-designed studies are required to validate the aforementioned PGT platform.

scholarly journals Egészséges gyermek születése karyomapping eljárással történő preimplantációs genetikai diagnózist követően

2016 ◽  
Vol 157 (51) ◽  
pp. 2048-2050
Author(s):  
László Nánássy ◽  
Gyöngyvér Téglás ◽  
Marianna Csenki ◽  
Attila Vereczkey
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Assisted Reproductive Technologies ◽  
Single Nucleotide Polymorphism Array ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Reproductive Technologies ◽  
Congenital Glaucoma ◽  
Primary Congenital Glaucoma ◽  
A Genome ◽  
Gene Defects

Abstract: Preimplantation genetic diagnosis for single gene defects is a well established method in assisted reproductive technologies. Karyomapping is a genome wide parental haplotyping using a high density single nucleotide polymorphism array that allows the diagnosis of any single gene defects. A couple with an affected child with primary congenital glaucoma attended at our clinic. Six oocyte-cumulus-complex was retrieved and all three mature oocytes were inseminated. One zygote showed the signs of normal fertilization and was cultured for five days. Trophectoderm biopsy and karyomapping analysis were carried out. Result showed a heterozygous carrier for primary congenital glaucoma. Embryo was thawed and transferred and a healthy girl was delivered at term. Here we report the first live birth following in vitro fertilization combined with preimplantation genetic diagnosis using karyomapping in Hungary. Karyomapping is able to accurately detect single gene disorders from a limited amount of samples without a significant preclinical workup. Orv. Hetil., 2016, 157(51), 2048–2050.

scholarly journals A preimplantation genetic testing of monogenic diseases. Description of clinical case

2018 ◽  
Vol 67 (1) ◽  
pp. 92-95
Author(s):  
Igor Yu. Kogan ◽  
Pavel P. Iakovlev ◽  
Alexander M. Gzgzyan ◽  
Irina D. Mekina ◽  
Marianna A. Maretina ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Clinical Case ◽  
Single Gene ◽  
Structural Rearrangements ◽  
Preimplantation Genetic Testing ◽  
Smn1 Gene ◽  
Subsequent Birth ◽  
Monogenic Diseases ◽  
The Family ◽  
Gene Defects

Preimplantation genetic testing performed to analyze the chromosomal structural rearrangements, monogenic/single gene defects and aneuploidies. The aim of this study is to show the discussion of a clinical case of preimplantation genetic testing in the family of SMN1 gene mutation carriers with the subsequent birth of a healthy child.

scholarly journals Genetic Testing Contributes to Diagnosis in Cerebral Palsy: Aicardi-Goutières Syndrome as an Example

2021 ◽  
Vol 12 ◽  
Author(s):  
Diane Beysen ◽  
Chania De Cordt ◽  
Charlotte Dielman ◽  
Benson Ogunjimi ◽  
Julie Dandelooy ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Genetic Testing ◽  
Single Gene ◽  
Neurodevelopmental Disorder ◽  
Diagnostic Testing ◽  
Copy Number Variants ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
Birth Asphyxia ◽  
Spastic Cerebral Palsy

Cerebral palsy (CP) is a non-progressive neurodevelopmental disorder characterized by motor impairments, often accompanied by co-morbidities such as intellectual disability, epilepsy, visual and hearing impairment and speech and language deficits. Despite the established role of hypoxic–ischemic injury in some CP cases, several studies suggest that birth asphyxia is actually an uncommon cause, accounting for <10% of CP cases. For children with CP in the absence of traditional risk factors, a genetic basis to their condition is increasingly suspected. Several recent studies indeed confirm copy number variants and single gene mutations with large genetic heterogeneity as an etiology in children with CP. Here, we report three patients with spastic cerebral palsy and a genetically confirmed diagnosis of Aicardi-Goutières syndrome (AGS), with highly variable phenotypes ranging from clinically suggestive to non-specific symptomatology. Our findings suggest that AGS may be a rather common cause of CP, that frequently remains undiagnosed without additional genetic testing, as in only one case a clinical suspicion of AGS was raised. Our data show that a diagnosis of AGS must be considered in cases with spastic CP, even in the absence of characteristic brain abnormalities. Importantly, a genetic diagnosis of AGS may have significant therapeutic consequences, as targeted therapies are being developed for type 1 interferonopathies, the group of diseases to which AGS belongs. Our findings demonstrate the importance of next generation sequencing in CP patients without an identifiable cause, since targeted diagnostic testing is hampered by the often non-specific presentation.

Sign in / Sign up

Export Citation Format

Share Document