Prospective evaluation of the clinical utility of whole-exome sequencing using buccal swabbing for undiagnosed rare diseases

• 영문명: Prospective evaluation of the clinical utility of whole-exome sequencing using buccal swabbing for undiagnosed rare diseases
• 발행기관: 대한의학유전학회
• 저자명: Chong Kun Cheon Yong Beom Shin Soo-Yeon Kim Go Hun Seo Hane Lee Changwon Keum Seung Hwan Oh
• 간행물 정보: 『대한의학유전학회지』제19권 제2호, 76~84쪽, 전체 9쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2022.12.31

영문 초록

Purpose: Whole-exome sequencing (WES) has been a useful tool for novel gene discovery of various disease categories, further increasing the diagnostic yield. This study aimed to investigate the clinical utility of WES prospectively in undiagnosed genetic diseases. Materials and Methods: WES tests were performed on 110 patients (age range, 0-28 years) with suspected rare genetic diseas-es. WES tests were performed at a single reference laboratory and the variants reported were reviewed by clinical geneticists, pediatricians, neurologists, and laboratory physicians. Results: The patients’ symptoms varied with abnormalities in the head or neck, including facial dysmorphism, being the most common, identified in 85.4% of patients, followed by abnormalities in the nervous system (83.6%). The average number of systems manifesting phenotypic abnormalities per patient was 3.9±1.7. The age at presentation was 2.1±2.7 years old (range, 0-15 years), and the age at WES testing was 6.7±5.3 years (range, 0-28 years). In total, WES test reported 100 pathogenic/likely pathogenic variants or variants of uncertain significance for 79 out of 110 probands (71.8%). Of the 79 patients with positive or inconclusive calls, 55 (50.0%) patients were determined to have good genotype-phenotype correlations after careful re-view. Further clinical reassessment and family member testing determined 45 (40.9%) patients to have been identified with a molecular diagnosis. Conclusion: This study showed a 40.9% diagnostic yield for WES test for a heterogeneous patient cohort with suspected rare genetic diseases. WES could be the feasible genetic test modality to overcome the diversity and complexity of rare disease diagnostics.

목차

Introduction

Materials and Methods

Results

Discussion

Acknowledgements

Author’s Contributions

References

키워드

Exome sequencing Rare diseases Gene discovery