Estimating at-risk couple rates across 1000 exome sequencing data cohort for 176 genes and its importance relevance for health policies.
| Title: | Estimating at-risk couple rates across 1000 exome sequencing data cohort for 176 genes and its importance relevance for health policies. |
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| Authors: | Marinakis NM; Laboratory of Medical Genetics, Medical School, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. nikomari@med.uoa.gr.; Research University Institute for the Study and Prevention of Genetic and Malignant Disease of Childhood, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. nikomari@med.uoa.gr.; Tilemis FN; Laboratory of Medical Genetics, Medical School, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Veltra D; Laboratory of Medical Genetics, Medical School, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Research University Institute for the Study and Prevention of Genetic and Malignant Disease of Childhood, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Svingou M; Laboratory of Medical Genetics, Medical School, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Sofocleous C; Laboratory of Medical Genetics, Medical School, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Kekou K; Laboratory of Medical Genetics, Medical School, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Kosma K; Laboratory of Medical Genetics, Medical School, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Kampouraki A; Laboratory of Medical Genetics, Medical School, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Kontse C; Division of Endocrinology, Diabetes and Metabolism, St. Sophia's Children's Hospital, ENDO-ERN Center for Rare Paediatric Endocrine Diseases, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Fylaktou I; Division of Endocrinology, Diabetes and Metabolism, St. Sophia's Children's Hospital, ENDO-ERN Center for Rare Paediatric Endocrine Diseases, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Sertedaki A; Division of Endocrinology, Diabetes and Metabolism, St. Sophia's Children's Hospital, ENDO-ERN Center for Rare Paediatric Endocrine Diseases, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Kanaka-Gantenbein C; Division of Endocrinology, Diabetes and Metabolism, St. Sophia's Children's Hospital, ENDO-ERN Center for Rare Paediatric Endocrine Diseases, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Traeger-Synodinos J; Laboratory of Medical Genetics, Medical School, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Makrythanasis P; Laboratory of Medical Genetics, Medical School, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. pmakryth@med.uoa.gr.; Biomedical Research Foundation of the Academy of Athens, Athens, Greece. pmakryth@med.uoa.gr.; Department of Genetic Medicine and Development, Medical School, University of Geneva, Geneva, Switzerland. pmakryth@med.uoa.gr. |
| Source: | European journal of human genetics : EJHG [Eur J Hum Genet] 2025 Jan; Vol. 33 (1), pp. 65-71. Date of Electronic Publication: 2024 Nov 02. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9302235 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5438 (Electronic) Linking ISSN: 10184813 NLM ISO Abbreviation: Eur J Hum Genet Subsets: MEDLINE |
| Imprint Name(s): | Publication: : London : Nature Publishing Group; Original Publication: Basel ; New York : Karger, [1992- |
| MeSH Terms: | Genetic Testing*/methods ; Genetic Testing*/standards ; Genetic Carrier Screening*/methods ; Genetic Carrier Screening*/standards ; Exome Sequencing*; Greece/epidemiology ; Humans ; Female ; Male ; Health Policy ; Heterozygote ; Exome |
| Abstract: | The development of high-throughput technologies has enabled Expanded Carrier screening (ECS) as a more comprehensive and extensive approach for high-risk populations. The available methods of ECS are population-targeted gene-panels according to ethnicity, however these panels should be planned according to a real-world data evaluation. In this study, we estimate the frequency of pathogenic variants for autosomal-recessive and X-linked conditions in Exome Sequencing-ES data for a 176 gene panel proposed from ACMG and ACOG in a Greek cohort. ES data from 1000 unrelated individuals was evaluated for pathogenic SNVs and CNVs. Variants were filtered using 5% Minor Frequency Allele (MAF), ClinVar submissions, and classification with ACMG criteria. For the at-risk couple rate, we hypothesized that both parents carried variants in the same gene. It is noted that many common conditions (hemoglobinopathies, SMA, Fragile-X) may escape NGS-based detection as they require alternative methods for optimal detection. Amongst 1000 participants, 32% were heterozygous for at least one disorder and 14% for two or more, whereby 393 unique pathogenic/likely pathogenic heterozygous variants were identified. We calculated that 1.6% of couples have a risk for at least one AR condition, which means that for 85,000 births per year, 1380 couples require genetic counseling. This study provides data confirming that the ACMG/ACOG ECS list of 176 genes is suitable for carrier screening in Greece, and aids counseling prospective parents for residual risk, however it should be supported by appropriate interpretation and reproductive options, as well as ancillary genetic testing methods.; (© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.) |
| Competing Interests: | Competing interests: The authors declare no competing interests. Ethical approval: Ethical approval was obtained from the Bioethics and Ethics committee of the St. Sophia’s Children’s Hospital, National and Kapodistrian University of Athens (Approval number: 3669/12-02-18, 22140/10-09/2024). Written informed consent was obtained from all participants or their legal guardians. |
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| Entry Date(s): | Date Created: 20241103 Date Completed: 20250109 Latest Revision: 20260102 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11711610 |
| DOI: | 10.1038/s41431-024-01726-4 |
| PMID: | 39488673 |
| Database: | MEDLINE |
Journal Article