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Whole exome sequencing reveal 83 novel Mendelian disorders carrier P/LP variants in Chinese adult patients

Journal of Human Genetics volume 68, pages 737–743 (2023)Cite this article

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Abstract

Carrier screening can identify people at risk of conceiving pregnancies affected with inherited genetic disorders or who have a genetic disorder with late or variable onset. Carrier screening based on whole exome sequencing (WES) data can offer more comprehensive assessment than on-target carrier screening tests. A total of 224 Chinese adult patients WES data was analyzed, except positive variants associated with the patients’ major complaint, 378 pathogenic (P) and “likely pathogenic” (LP) variants from 175 adult patients were identified. Whole exome-wide frequency of carriers for Mendelian disorders in Chinese adult patients was about 78.13% in this study, which was lower than the previously reported carrier frequency in healthy population. Contrary to expectations, the number of P or LP variants did not increase with larger chromosome size or decrease with smaller chromosome size. Totally 83 novel P or LP variants were identified which could further expand the carrier variants spectrum of the Chinese population. GJB2: NM_004004.6:c.299_300delAT:p.His100fs*14 and C6:NM_000065.4:c.654T>A:p.Cys218* were found in two or more patients, which might be two underestimated carrier variants in Chinese population. We also found 9 late-onset or atypical symptoms autosomal/X-linked dominant Mendelian disorders causative genes, which were easily overlooked during pathogenicity analysis. These results can provide a strong basis for preventing and avoiding the prevalence rates of birth defects and reducing social and family burdens. By comparing with three different expanded carrier screening gene panels, we further confirmed carrier screening based on WES could offer more comprehensive assessment and WES was applicable for carrier screening.

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The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.

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Acknowledgements

First, we sincerely thank all the participants in this study for their cooperation and support. We thank many doctors from our department of echocardiography and neurology, who contributed to the recruitment and clinical follow-up. All authors read and approved the final manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81972000, No. 82172348, No. 81902139, No. 82202607), the constructing project of clinical key disciplines in Shanghai (No. shslczdzk03302), Shanghai Medical Key Specialty (ZK2019B28), the key medical and health projects of Xiamen (No. YDZX20193502000002).

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  1. These authors contributed equally: Li Zhang, Li Yu.

Authors and Affiliations

  1. Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China

    Li Zhang, Li Yu, Baishen Pan, Wei Guo, Chunyan Zhang & Beili Wang

  2. Department of Echocardiography, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China

    Xianhong Shu

  3. Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China

    Jing Ding

  4. Department of Cardiology Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China

    Jingmin Zhou

  5. Department of Neurology, Zhongshan Hospital, State Key Laboratory, Fudan University, Shanghai, China

    Chunjiu Zhong

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Contributions

LZ and LY wrote the main manuscript text and prepared Figs. 1–3. XS, JD, JZ, and CZ provided clinical samples, BW, CZ, WG, and BP designed the research. All authors reviewed the manuscript.

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Correspondence to Chunyan Zhang or Beili Wang.

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Zhang, L., Yu, L., Shu, X. et al. Whole exome sequencing reveal 83 novel Mendelian disorders carrier P/LP variants in Chinese adult patients. J Hum Genet 68, 737–743 (2023). https://doi.org/10.1038/s10038-023-01179-5

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