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Beyond CHD7 gene: unveiling genetic diversity in clinically suspected CHARGE syndrome

Journal of Human Genetics volume 70, pages 243–248 (2025)Cite this article

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Abstract

The Verloes or Hale diagnostic criteria have been applied for diagnosing CHARGE syndrome in suspected patients. This study was conducted to evaluate the diagnostic rate of CHD7 according to these diagnostic criteria in suspected patients and also to investigate other genetic defects in CHD7-negative patients. The clinical findings and the results of genetic testing of CHD7, chromosome microarray, exome sequencing, or genome sequencing of 59 subjects were reviewed. CHD7 pathogenic variants were identified in 78% of 46 subjects who met either the Verloes or Hale diagnostic criteria and in 87% of 38 subjects who met both criteria, whereas no CHD7 variant was detected in 13 subjects who met neither criterion. Among 23 patients without the CHD7 variant, six genetic diseases were identified in 7 patients, including Wolf–Hirschhorn syndrome, 1q21 deletion syndrome, 19q13 microdeletion, and pathogenic variants in PLCB4, TRRAP, and OTX2. Based on these comprehensive analyses, the overall diagnostic rate was 73% for seven different genetic diseases. This study emphasizes the importance of comprehensive clinical and genetic evaluation in patients with clinically suspected CHARGE syndrome, recognizing the overlapping phenotypes in other rare genetic disorders.

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The data that support the findings of this study can be obtained from the corresponding author upon reasonable request.

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Acknowledgements

Conception or design: DK and BHL. Acquisition, analysis, or interpretation of data: DK, JHY, HB, SH, GHS, JYK, YSJ, HSD, SK, IHC, GHK, JHK, JHC, and BHL. Drafting or revising the work: DK and BHL. Final approval of the manuscript: DK, JHY, HB, SH, GHS, JYK, YSJ, HSD, SK, IHC, GHK, JHK, JHC, and BHL.

Funding

This research was supported by a grant of the Research Program funded by the Korea Disease Control and Prevention Agency, Republic of Korea (2021-ER0402-00), the Asan Institute for Life Sciences (Seoul, Republic of Korea) (2024IP0076), 3Billions Inc. (Seoul, Republic of Korea), and Inocras Inc. (Daejeon, Republic of Korea).

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Authors and Affiliations

  1. Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Dohyung Kim, Ji-Hee Yoon, Hyunwoo Bae, Soojin Hwang, Ja Hye Kim, Jin-Ho Choi & Beom Hee Lee

  2. Medical Genetics Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Dohyung Kim, Ji-Hee Yoon, Hyunwoo Bae, Soojin Hwang, Gu-Hwan Kim, Ja Hye Kim, Jin-Ho Choi & Beom Hee Lee

  3. Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

    Ji-Hee Yoon

  4. Department of Pediatrics, Kyungpook National University Chilgok Hospital, Seoul, Republic of Korea

    Hyunwoo Bae

  5. Division of Medical genetics, 3billion Inc, Seoul, Republic of Korea

    Go Hun Seo

  6. Inocras Inc., Daejeon, Republic of Korea

    June-Young Koh & Young Seok Ju

  7. Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea

    Hyo-Sang Do & Soyoung Kim

  8. Department of Genetic Counseling, University of Ulsan College of Medicine, Seoul, Republic of Korea

    In Hee Choi

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  1. Dohyung Kim
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Correspondence to Beom Hee Lee.

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Kim, D., Yoon, JH., Bae, H. et al. Beyond CHD7 gene: unveiling genetic diversity in clinically suspected CHARGE syndrome. J Hum Genet 70, 243–248 (2025). https://doi.org/10.1038/s10038-025-01325-1

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