Exome and genome sequencing for diagnosing patients with suspected rare genetic disease

• 영문명: Exome and genome sequencing for diagnosing patients with suspected rare genetic disease
• 발행기관: 대한의학유전학회
• 저자명: Go Hun Seo Hane Lee
• 간행물 정보: 『대한의학유전학회지』제20권 제2호, 31~38쪽, 전체 8쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2023.12.31

영문 초록

Rare diseases, even though defined as fewer than 20,000 in South Korea, with over 8,000 rare Mendelian disorders having been identified, they collectively impact 6-8% of the global population. Many of the rare diseases pose significant challenges to patients, patients’ families, and the healthcare system. The diagnostic journey for rare disease patients is often lengthy and arduous, hampered by the genetic diversity and phenotypic complexity of these conditions. With the advent of nextgeneration sequencing technology and clinical implementation of exome sequencing (ES) and genome sequencing (GS), the diagnostic rate for rare diseases is 25-50% depending on the disease category. It is also allowing more rapid new gene-disease association discovery and equipping us to practice precision medicine by offering tailored medical management plans, early intervention, family planning options. However, a substantial number of patients remain undiagnosed, and it could be due to several factors. Some may not have genetic disorders. Some may have disease-causing variants that are not detectable or interpretable by ES and GS. It's also possible that some patient might have a disease-causing variant in a gene that hasn't yet been linked to a disease. For patients who remain undiagnosed, reanalysis of existing data has shown promises in providing new molecular diagnoses achieved by new gene-disease associations, new variant discovery, and variant reclassification, leading to a 5-10% increase in the diagnostic rate. More advanced approach such as long-read sequencing, transcriptome sequencing and integration of multi-omics data may provide potential values in uncovering elusive genetic causes.

목차

Introduction

Indication for Exome and Genome Sequencing

Testing Workflow of Exome and Genome Sequencing

Diagnostic Yield and Technical Limitation of Exome and Genome Sequencing

Next Steps for Exome/Genome-Negative Patients

Conclusion

Acknowledgements

Funding

Authors' Contributions

References

키워드

Rare diseases Exome sequencing Whole genome sequencing