A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies
Abstract Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, pe...
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Nature Portfolio
2021
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oai:doaj.org-article:e733bb6318cd4cbcadc0d78a11b7a3cd2021-12-02T17:17:39ZA single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies10.1038/s41598-021-98646-w2045-2322https://doaj.org/article/e733bb6318cd4cbcadc0d78a11b7a3cd2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98646-whttps://doaj.org/toc/2045-2322Abstract Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, performed at a tertiary center in Israel, over a 3-year period (2018–2020). Probands presented with (1) moderate-to-profound global developmental delay (GDD)/intellectual disability (ID); or (2) mild GDD/ID with epilepsy or congenital anomaly; and/or (3) MCA. Subjects with normal chromosomal microarray analysis who met inclusion criteria were included, totaling 280 consecutive cases. Trio ES (proband and parents) was the default option. In 252 cases (90.0%), indication of NDD was noted. Most probands were males (62.9%), and their mean age at ES submission was 9.3 years (range 1 month to 51 years). Molecular diagnosis was reached in 109 probands (38.9%), mainly due to de novo variants (91/109, 83.5%). Disease-causing variants were identified in 92 genes, 15 of which were implicated in more than a single case. Male sex, families with multiple-affected members and premature birth were significantly associated with lower ES yield (p < 0.05). Other factors, including MCA and coexistence of epilepsy, autism spectrum disorder, microcephaly or abnormal brain magnetic resonance imaging findings, were not associated with the yield. To conclude, our findings support the utility of clinical ES in a real-world setting, as part of a publicly funded genetic workup for individuals with GDD/ID and/or MCA.Ben Pode-ShakkedOrtal BarelAmihood SingerMiriam RegevHana PoranAviva EliyahuYael FinezilberMeirav SegevMichal BerkenstadtHagith YonathHaike Reznik-WolfYael GazitOdelia ChorinGali HeimerLidia V. GabisMichal TzadokAndreea NissenkornOmer Bar-YosefEfrat Zohar-DayanBruria Ben-ZeevNofar MorNitzan KolOmri NayshoolNoam ShimshovizIfat Bar-JosephDina Marek-YagelElisheva JavaskyReviva EinyMoran GalJulia Grinshpun-CohenMordechai ShohatDan DominissiniAnnick Raas-RothschildGideon RechaviElon PrasLior GreenbaumNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021) |
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Medicine R Science Q Ben Pode-Shakked Ortal Barel Amihood Singer Miriam Regev Hana Poran Aviva Eliyahu Yael Finezilber Meirav Segev Michal Berkenstadt Hagith Yonath Haike Reznik-Wolf Yael Gazit Odelia Chorin Gali Heimer Lidia V. Gabis Michal Tzadok Andreea Nissenkorn Omer Bar-Yosef Efrat Zohar-Dayan Bruria Ben-Zeev Nofar Mor Nitzan Kol Omri Nayshool Noam Shimshoviz Ifat Bar-Joseph Dina Marek-Yagel Elisheva Javasky Reviva Einy Moran Gal Julia Grinshpun-Cohen Mordechai Shohat Dan Dominissini Annick Raas-Rothschild Gideon Rechavi Elon Pras Lior Greenbaum A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies |
| description |
Abstract Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, performed at a tertiary center in Israel, over a 3-year period (2018–2020). Probands presented with (1) moderate-to-profound global developmental delay (GDD)/intellectual disability (ID); or (2) mild GDD/ID with epilepsy or congenital anomaly; and/or (3) MCA. Subjects with normal chromosomal microarray analysis who met inclusion criteria were included, totaling 280 consecutive cases. Trio ES (proband and parents) was the default option. In 252 cases (90.0%), indication of NDD was noted. Most probands were males (62.9%), and their mean age at ES submission was 9.3 years (range 1 month to 51 years). Molecular diagnosis was reached in 109 probands (38.9%), mainly due to de novo variants (91/109, 83.5%). Disease-causing variants were identified in 92 genes, 15 of which were implicated in more than a single case. Male sex, families with multiple-affected members and premature birth were significantly associated with lower ES yield (p < 0.05). Other factors, including MCA and coexistence of epilepsy, autism spectrum disorder, microcephaly or abnormal brain magnetic resonance imaging findings, were not associated with the yield. To conclude, our findings support the utility of clinical ES in a real-world setting, as part of a publicly funded genetic workup for individuals with GDD/ID and/or MCA. |
| format |
article |
| author |
Ben Pode-Shakked Ortal Barel Amihood Singer Miriam Regev Hana Poran Aviva Eliyahu Yael Finezilber Meirav Segev Michal Berkenstadt Hagith Yonath Haike Reznik-Wolf Yael Gazit Odelia Chorin Gali Heimer Lidia V. Gabis Michal Tzadok Andreea Nissenkorn Omer Bar-Yosef Efrat Zohar-Dayan Bruria Ben-Zeev Nofar Mor Nitzan Kol Omri Nayshool Noam Shimshoviz Ifat Bar-Joseph Dina Marek-Yagel Elisheva Javasky Reviva Einy Moran Gal Julia Grinshpun-Cohen Mordechai Shohat Dan Dominissini Annick Raas-Rothschild Gideon Rechavi Elon Pras Lior Greenbaum |
| author_facet |
Ben Pode-Shakked Ortal Barel Amihood Singer Miriam Regev Hana Poran Aviva Eliyahu Yael Finezilber Meirav Segev Michal Berkenstadt Hagith Yonath Haike Reznik-Wolf Yael Gazit Odelia Chorin Gali Heimer Lidia V. Gabis Michal Tzadok Andreea Nissenkorn Omer Bar-Yosef Efrat Zohar-Dayan Bruria Ben-Zeev Nofar Mor Nitzan Kol Omri Nayshool Noam Shimshoviz Ifat Bar-Joseph Dina Marek-Yagel Elisheva Javasky Reviva Einy Moran Gal Julia Grinshpun-Cohen Mordechai Shohat Dan Dominissini Annick Raas-Rothschild Gideon Rechavi Elon Pras Lior Greenbaum |
| author_sort |
Ben Pode-Shakked |
| title |
A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies |
| title_short |
A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies |
| title_full |
A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies |
| title_fullStr |
A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies |
| title_full_unstemmed |
A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies |
| title_sort |
single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/e733bb6318cd4cbcadc0d78a11b7a3cd |
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