Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disorders
Abstract We investigated the effectiveness of exome sequencing (ES) in diagnosing ethnically diverse patients with rare genetic disorders. A total of 18,994 patients referred to a single reference laboratory for ES between 2020 and 2022 were studied for the diagnostic rate and factors influencing th...
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Nature Portfolio
2025-01-01
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| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-024-00455-3 |
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| author | Heonjong Han Go Hun Seo Seong-In Hyun Kisang Kwon Seung Woo Ryu Rin Khang Eugene Lee JiHye Kim Yongjun Song Won Chan Jeong Joohyun Han Dong-wook Kim Soyeon Yang Sohyun Lee Sohyun Jang Jungsul Lee Hane Lee |
| author_facet | Heonjong Han Go Hun Seo Seong-In Hyun Kisang Kwon Seung Woo Ryu Rin Khang Eugene Lee JiHye Kim Yongjun Song Won Chan Jeong Joohyun Han Dong-wook Kim Soyeon Yang Sohyun Lee Sohyun Jang Jungsul Lee Hane Lee |
| author_sort | Heonjong Han |
| collection | DOAJ |
| description | Abstract We investigated the effectiveness of exome sequencing (ES) in diagnosing ethnically diverse patients with rare genetic disorders. A total of 18,994 patients referred to a single reference laboratory for ES between 2020 and 2022 were studied for the diagnostic rate and factors influencing the diagnostic rate. The overall diagnostic rate was 31.8%. Dermatological disorders, skeletal disorders, and neurodevelopmental disorders disease categories, early age-of-onset, presence of consanguinity, and the presence of parental sequencing data were found to be correlated with a higher diagnostic rate. Nearly 68K variants were identified in our dataset at a higher frequency than that observed in gnomAD 4.0. Of these, 507 variants could be classified as likely benign, representing 0.04% of non-benign variants in ClinVar (507/1,433,904) and 0.20% of the non-benign ClinVar variants observed at least once in our cohort (507/276,777). The overall diagnostic rate is comparable to that observed in other large cohort studies with less diverse ethnic backgrounds. |
| format | Article |
| id | doaj-art-30730b989b0d4e08ad19e3e2c5925e92 |
| institution | Kabale University |
| issn | 2056-7944 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj-art-30730b989b0d4e08ad19e3e2c5925e922025-01-26T12:45:44ZengNature Portfolionpj Genomic Medicine2056-79442025-01-011011910.1038/s41525-024-00455-3Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disordersHeonjong Han0Go Hun Seo1Seong-In Hyun2Kisang Kwon3Seung Woo Ryu4Rin Khang5Eugene Lee6JiHye Kim7Yongjun Song8Won Chan Jeong9Joohyun Han10Dong-wook Kim11Soyeon Yang12Sohyun Lee13Sohyun Jang14Jungsul Lee15Hane Lee163billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.3billion, Inc.Abstract We investigated the effectiveness of exome sequencing (ES) in diagnosing ethnically diverse patients with rare genetic disorders. A total of 18,994 patients referred to a single reference laboratory for ES between 2020 and 2022 were studied for the diagnostic rate and factors influencing the diagnostic rate. The overall diagnostic rate was 31.8%. Dermatological disorders, skeletal disorders, and neurodevelopmental disorders disease categories, early age-of-onset, presence of consanguinity, and the presence of parental sequencing data were found to be correlated with a higher diagnostic rate. Nearly 68K variants were identified in our dataset at a higher frequency than that observed in gnomAD 4.0. Of these, 507 variants could be classified as likely benign, representing 0.04% of non-benign variants in ClinVar (507/1,433,904) and 0.20% of the non-benign ClinVar variants observed at least once in our cohort (507/276,777). The overall diagnostic rate is comparable to that observed in other large cohort studies with less diverse ethnic backgrounds.https://doi.org/10.1038/s41525-024-00455-3 |
| spellingShingle | Heonjong Han Go Hun Seo Seong-In Hyun Kisang Kwon Seung Woo Ryu Rin Khang Eugene Lee JiHye Kim Yongjun Song Won Chan Jeong Joohyun Han Dong-wook Kim Soyeon Yang Sohyun Lee Sohyun Jang Jungsul Lee Hane Lee Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disorders npj Genomic Medicine |
| title | Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disorders |
| title_full | Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disorders |
| title_fullStr | Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disorders |
| title_full_unstemmed | Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disorders |
| title_short | Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disorders |
| title_sort | exome sequencing of 18 994 ethnically diverse patients with suspected rare mendelian disorders |
| url | https://doi.org/10.1038/s41525-024-00455-3 |
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