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The Korean Genetic Diagnosis Program for Rare Disease Phase II: outcomes of a 6-year national project

European Journal of Human Genetics volume 31, pages 1147–1153 (2023)Cite this article

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Abstract

The Korean Genetic Diagnosis Program for Rare Disease (KGDP) enrolled 1890 patients with rare diseases between March 2017 and October 2022. Children and adolescents accounted for the majority of the patients, and systemic disease was the most common presenting symptom. The exome-based virtual disease-specific multigene panel was the most frequently used analytical method, with an overall diagnostic yield of 33.3%. A total of 629 positive cases were diagnosed, involving 297 genes. All 297 genes identified in these cases were confirmed to be known genes listed in the OMIM database. The nationwide KGDP network and its cooperation with the Korean Undiagnosed Diseases Program (KUDP) provide a more comprehensive genetic analysis of undiagnosed cases. The partnership between the KGDP and KUDP has the potential to improve the diagnosis and treatment options for patients. In conclusion, KGDP serves as the primary access point or gateway to KUDP.

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Fig. 1: Assessing variations in genetic diversity among confirmed cases grouped by age and primary symptom presentation.
Fig. 2: Location of 51 participating clinical sites in Korea.
Fig. 3: Schematic workflow of the Korean Genetic Diagnosis Program for Rare Diseases (KGDP).

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Hayashi S, Umeda T. 35 years of Japanese policy on rare diseases. Lancet 2008;372:889–90.

    Article  PubMed  Google Scholar 

  2. Puiu M, Dan D. Rare diseases, from European resolutions and recommendations to actual measures and strategies. Maedica. 2010;5:128–31.

    PubMed  PubMed Central  Google Scholar 

  3. Valdez R, Ouyang L, Bolen J. Public health and rare diseases: oxymoron no more. Prev Chronic Dis. 2016;13:E05.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Marwaha S, Knowles JW, Ashley EA. A guide for the diagnosis of rare and undiagnosed disease: beyond the exome. Genome Med. 2022;14:23.

    Article  PubMed  PubMed Central  Google Scholar 

  5. The Lancet Diabetes Endocrinology. Spotlight on rare diseases. Lancet Diabetes Endocrinol. 2019;7:75.

    Article  CAS  PubMed  Google Scholar 

  6. Navarrete-Opazo AA, Singh M, Tisdale A, Cutillo CM, Garrison SR. Can you hear us now? The impact of health-care utilization by rare disease patients in the United States. Genet Med. 2021;23:2194–201.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Adachi T, Kawamura K, Furusawa Y, Nishizaki Y, Imanishi N, Umehara S, et al. Japan’s initiative on rare and undiagnosed diseases (IRUD): towards an end to the diagnostic odyssey. Eur J Hum Genet. 2017;25:1025–8.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Beaulieu CL, Majewski J, Schwartzentruber J, Samuels ME, Fernandez BA, Bernier FP, et al. FORGE Canada Consortium: outcomes of a 2-year national rare-disease gene-discovery project. Am J Hum Genet. 2014;94:809–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kim SY, Lim BC, Lee JS, Kim WJ, Kim H, Ko JM, et al. The Korean undiagnosed diseases program: lessons from a one-year pilot project. Orphanet J Rare Dis. 2019;14:68.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lochmuller H, Torrent IFJ, Le Cam Y, Jonker AH, Lau LP, Baynam G, et al. The International Rare Diseases Research Consortium: policies and guidelines to maximize impact. Eur J Hum Genet. 2017;25:1293–302.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kim MJ, Lee S, Yun H, Cho SI, Kim B, Lee JS, et al. Consistent count region-copy number variation (CCR-CNV): an expandable and robust tool for clinical diagnosis of copy number variation at the exon level using next-generation sequencing data. Genet Med. 2022;24:663–72.

    Article  CAS  PubMed  Google Scholar 

  13. Kim SY, Lee S, Woo H, Han J, Ko YJ, Shim Y, et al. The Korean undiagnosed diseases program phase I: expansion of the nationwide network and the development of long-term infrastructure. Orphanet J Rare Dis. 2022;17:372.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Keicho N, Hijikata M, Morimoto K, Homma S, Taguchi Y, Azuma A, et al. Primary ciliary dyskinesia caused by a large homozygous deletion including exons 1-4 of DRC1 in Japanese patients with recurrent sinopulmonary infection. Mol Genet Genom Med. 2020;8:e1033.

    Article  Google Scholar 

  15. Morimoto K, Hijikata M, Zariwala MA, Nykamp K, Inaba A, Guo TC, et al. Recurring large deletion in DRC1 (CCDC164) identified as causing primary ciliary dyskinesia in two Asian patients. Mol Genet Genom Med. 2019;7:e838.

    Article  Google Scholar 

  16. Takeuchi K, Xu Y, Kitano M, Chiyonobu K, Abo M, Ikegami K, et al. Copy number variation in DRC1 is the major cause of primary ciliary dyskinesia in the Japanese population. Mol Genet Genom Med. 2020;8:e1137.

    Article  CAS  Google Scholar 

  17. Kim MJ, Kim S, Chae SW, Lee S, Yoon JG, Kim B, et al. Prevalence and founder effect of DRC1 exon 1-4 deletion in Korean patients with primary ciliary dyskinesia. J Hum Genet. 2023;68:369–74.

    Article  CAS  PubMed  Google Scholar 

  18. Srivastava S, Love-Nichols JA, Dies KA, Ledbetter DH, Martin CL, Chung WK, et al. Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genet Med. 2019;21:2413–21.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Shickh S, Gutierrez Salazar M, Zakoor KR, Lazaro C, Gu J, Goltz J, et al. Exome and genome sequencing in adults with undiagnosed disease: a prospective cohort study. J Med Genet. 2021;58:275–83.

    Article  CAS  PubMed  Google Scholar 

  20. Han SR, Lee YA, Shin CH, Yang SW, Lim BC, Cho TJ, et al. Clinical and molecular characteristics of GNAS inactivation disorders observed in 18 Korean patients. Exp Clin Endocrinol Diabetes. 2021;129:118–25.

    Article  CAS  PubMed  Google Scholar 

  21. Kim HY, Shin CH, Lee YA, Shin CH, Kim GH, Ko JM. Deciphering epigenetic backgrounds in a Korean cohort with Beckwith-Wiedemann syndrome. Ann Lab Med. 2022;42:668–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kim B, Kim MJ, Hur K, Jo SJ, Ko JM, Park SS, et al. Clinical and genetic profiling of nevoid basal cell carcinoma syndrome in Korean patients by whole-exome sequencing. Sci Rep. 2021;11:1163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by a grant (6500-6534-306) from the Korea Disease Control and Prevention Agency from 2021. Prior to this, from 2020 and earlier, our research was funded by a grant (4860-306-320) from the Korea Centers for Disease Control and Prevention.

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Authors and Affiliations

  1. Department of Genomic Medicine, Seoul National University Hospital, Seoul, Korea

    Man Jin Kim, Jangsup Moon & Jong-Hee Chae

  2. Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

    Boram Kim, Heerah Lee, Jee-Soo Lee, Seung Won Chae, Ho Seob Shin, Sung Im Cho, Sung Sup Park & Moon-Woo Seong

  3. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

    Seung Won Chae

  4. Department of Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

    Soo Yeon Kim, Byung Chan Lim, Jung Min Ko & Jong-Hee Chae

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  1. Man Jin Kim
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Contributions

Concept and design: MJK and MWS. Acquisition, analysis, or interpretation of data: all authors. Drafting of the manuscript: MJK and MWS. Statistical analysis: MJK. Obtained funding: MWS. Review of the manuscript: all authors. Supervision: MWS.

Corresponding author

Correspondence to Moon-Woo Seong.

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The authors declare no competing interests.

Ethical approval

All study procedures were approved by the Institutional Review Board of SNUH (IRB number: 2212-114-1389), and the study adhered to the Declaration of Helsinki for biomedical research involving human subjects.

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Kim, M.J., Kim, B., Lee, H. et al. The Korean Genetic Diagnosis Program for Rare Disease Phase II: outcomes of a 6-year national project. Eur J Hum Genet 31, 1147–1153 (2023). https://doi.org/10.1038/s41431-023-01415-8

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