Clinical utility of genome sequencing in rare diseases: lessons from a single-center study of 1,452 Korean families

Genome sequencing (GS) was applied to 3317 individuals from 1452 Korean families with suspected rare genetic disorders to assess diagnostic yield and clinical utility. Patients were categorized into 16 clinical subgroups with curated phenotypes, and variant interpretation was refined by post-analytic phenotype matching. A molecular diagnosis was achieved in 46.2% of families, influencing clinical management in 18.5% of diagnosed cases. Family-based GS had a higher yield than singleton testing (48.5% vs. 41.5%). Neuromuscular and neurodevelopmental disorders showed the highest yields. GS-specific variant types, including deep intronic, noncoding, complex structural variants, and tandem repeat expansions, accounted for 14.6% of diagnoses. Secondary findings were identified in 4.3% of individuals. Novel disease-associated genes such as RYBP, DNAJA3, CAMK2D, and small nuclear RNA genes were also reported. These results highlight the diagnostic power of GS and support its use as a first-tier test, especially in underrepresented populations.

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Publication Details

Journal
npj Genomic Medicine
Published
2025-12-08
DOI
https://doi.org/10.1038/s41525-025-00538-9
Citations
1
Primary Topic
Genomics and Rare Diseases
Type
article
Field-Weighted Citation Impact
1.82

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article

Clinical utility of genome sequencing in rare diseases: lessons from a single-center study of 1,452 Korean families

Jangsup Moon, Hane Lee, Seung Woo Ryu, S. Jang et al.
1 citations
npj Genomic Medicine
Genomics and Rare Diseases
1.82
article

Clinical utility of genome sequencing in rare diseases: lessons from a single-center study of 1,452 Korean families

Jangsup Moon, Hane Lee, Seung Woo Ryu, S. Jang, Songji Choi, Go Hun Seo, Seungbok Lee, Dal‐Seok Oh, Jong‐Hee Chae, Dongseok Moon, H.-J. Genie Chin, Seokhui Jang, Heonjong Han, Seoyun Jang, Jihye Kim, Seung Jae Lee, Soo Yeon Kim
article en
1 citations

Abstract

Genome sequencing (GS) was applied to 3317 individuals from 1452 Korean families with suspected rare genetic disorders to assess diagnostic yield and clinical utility. Patients were categorized into 16 clinical subgroups with curated phenotypes, and variant interpretation was refined by post-analytic phenotype matching. A molecular diagnosis was achieved in 46.2% of families, influencing clinical management in 18.5% of diagnosed cases. Family-based GS had a higher yield than singleton testing (48.5% vs. 41.5%). Neuromuscular and neurodevelopmental disorders showed the highest yields. GS-specific variant types, including deep intronic, noncoding, complex structural variants, and tandem repeat expansions, accounted for 14.6% of diagnoses. Secondary findings were identified in 4.3% of individuals. Novel disease-associated genes such as RYBP, DNAJA3, CAMK2D, and small nuclear RNA genes were also reported. These results highlight the diagnostic power of GS and support its use as a first-tier test, especially in underrepresented populations.

npj Genomic MedicineVol. 11(1)
Seoul National University Hospital (KR), Seoul National University Children's Hospital (KR)
Korea Disease Control and Prevention Agency, National Research Foundation, Ministry of Science and ICT, South Korea, Institute for Information and Communications Technology Promotion
Openalex Percentile: Top 11%
Genomics and Rare Diseases
1.82
DOIOpen Access PDFOpenAlex
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