Academic Journal
O-210 Detection of small copy number variations as incidental findings in PGT-A: clinical utility from a multisite experience including 12,157 patients
| العنوان: | O-210 Detection of small copy number variations as incidental findings in PGT-A: clinical utility from a multisite experience including 12,157 patients |
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| المؤلفون: | Iturriaga, A, Picchetta, L, Vega, C, Figliuzzi, M, Poli, M, Whitehead, C, Capalbo, A, Tao, X, Jobanputra, V, Loia, N, Jalas, C |
| المصدر: | Human Reproduction ; volume 38, issue Supplement_1 ; ISSN 0268-1161 1460-2350 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Obstetrics and Gynecology, Rehabilitation, Reproductive Medicine |
| الوصف: | Study question What is the technical accuracy and clinical utility of reporting small copy number variants (CNVs below 3Mb) detected by a targeted next-generation sequencing-based PGT-A platform? Summary answer Some pathogenic or likely pathogenic CNVs <3Mb can be accurately detected by this assay, increasing clinical utility of PGT-A for a subset of IVF patients. What is known already CNVs are linked to a wide range of phenotypes, spanning from syndromes that include reduced penetrance and variable expressivity to more severe phenotypes. Prenatally, the prevalence of pathogenic CNVs is approximately 1.5%. Most PGT-A platforms that rely on whole genome amplification and shallow sequencing have a resolution limit of 5-10 Mb, preventing the detection of smaller CNVs. Here, we report an innovative PGT-A assay that interrogates thousands of targeted sites in the genome to provide robust copy number analysis allowing for the identification of some small CNVs (incidental findings, IF), outside the primary scope of detecting whole-chromosome aneuploidies in PGT-A. Study design, size, duration Retrospective observational study performed between 2020-2022, involving 12,157 patients who underwent PGT-A performed by targeted-NGS (PGTseq-A) for whole chromosome and large segmental aneuploidies. If an IF < 3 Mb was detected in multiple embryos, the couple was advised to undergo follow-up analysis by chromosomal microarray (CMA) to confirm the parental origin of the CNV, define its breakpoints and determine whether it is classified as benign-likely benign (B/LB), variant of uncertain significance (VUS) or pathogenic-likely pathogenic (P/LP). Participants/materials, setting, methods The PGTseq-A assay employed amplifies 5,000 amplicons across the genome to evaluate copy number. Validation was performed using 5-cell samples from cell lines with known CNVs, and trophectoderm biopsies from embryos with known parental structural rearrangements. An IF was reported when a gain/loss of at least three ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/humrep/dead093.256 |
| الاتاحة: | http://dx.doi.org/10.1093/humrep/dead093.256 https://academic.oup.com/humrep/article-pdf/38/Supplement_1/dead093.256/50787318/dead093.256.pdf |
| Rights: | https://academic.oup.com/pages/standard-publication-reuse-rights |
| رقم الانضمام: | edsbas.6EB071B3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/humrep/dead093.256 |
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