Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disorders

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.

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Publication Details

Journal
npj Genomic Medicine
Published
2025-01-22
DOI
https://doi.org/10.1038/s41525-024-00455-3
Citations
6
Primary Topic
Genomics and Rare Diseases
Type
article
Field-Weighted Citation Impact
10.90
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article

Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disorders

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6 citations
npj Genomic Medicine
Genomics and Rare Diseases
10.90
article

Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disorders

Rin Khang, Hane Lee, Seung Woo Ryu, SoHyun Lee, Go Hun Seo, Soyeon Yang, Kisang Kwon, Yongjun Song, Jungsul Lee, Seong‐In Hyun, Heonjong Han, Won Chan Jeong, Dongwook Kim, Jihye Kim, Eugene Lee, Sohyun Jang, Joohyun Han
article en
6 citations

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.

npj Genomic MedicineVol. 10(1)
Korea Advanced Institute of Science and Technology (KR), Institute for Basic Science (KR), GeneMatrix (South Korea) (KR), Orion Corporation (United Kingdom) (GB)
Zero hunger
Openalex Percentile: Top 2%
Genomics and Rare Diseases
10.90
DOIOpen Access PDFOpenAlex
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