J Korean Med Assoc.  2023 Oct;66(10):613-623. 10.5124/jkma.2023.66.10.613.

Clinical applications of next-generation sequencing in the diagnosis of genetic disorders in Korea: a narrative review

• Yoon JG
• Kim MJ
• Kwon YJ
• Chae JH

• KMID: 2547251
• DOI: http://doi.org/10.5124/jkma.2023.66.10.613

Abstract

Background
Next-generation sequencing (NGS) technologies have revolutionized genetic testing and enabled efficient screening of various genetic conditions in clinical settings. However, the clinical application of genetic test results presents numerous significant challenges. This review aims to provide a comprehensive overview of key concepts for the clinical application of NGS, including (1) technical aspects and limitations, (2) variant classification, (3) clinical interpretation, (4) familial testing and genetic counseling, and (5) ethical considerations.
Current Concepts
In short-read-based NGS, several limitations exist in detecting genomic variations, including repetitive sequences or complex structural variations. The variant classification process can be influenced by suspected genomic conditions and the accessibility of genomic databases. Therefore, the final genetic diagnosis depends on the physician’s discretion, which relies on the genotype-phenotype correlations and reverse phenotyping through additional evaluations. Familial testing can help trace the origin of variants and allele segregation and aid in variant interpretation, risk assessment, disease prevention, and family planning. In addition to addressing the clinical impact of genetic results, genetic counselors should also consider potential consequences related to ethical, legal, and social issues, including family dynamics.
Discussion and Conclusion
NGS-based genetic testing is a promising diagnostic tool for genetic disorders, but proper variant interpretation and clinical evaluation are crucial for optimal clinical practice. Notably, ethical considerations and regulatory measures are required to prepare for the next era of genomic medicine.

Keyword

Genetic disorders; Next-generation sequencing; Genetic testing; Genetic counseling; 유전질환; 차세대 염기서열분석; 유전검사; 유전상담