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A genotype-first analysis in a cohort of Mullerian anomaly

Journal of Human Genetics volume 67, pages 347–352 (2022)Cite this article

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Abstract

Müllerian anomaly (M.A.) is a group of congenital anatomic abnormalities caused by aberrations of the development process of the Müllerian duct. M.A. can either be isolated or be involved in Mendelian syndromes, such as Dandy-Walker syndrome, Holt–Oram syndrome and Bardet–Biedl syndrome, which are often associated with both uterus and kidney malformations. In this study, we applied a genotype-first approach to analyze the whole-exome sequencing data of 492 patients with M.A. Six potential pathogenic variants were found in five genes previously related to female urogenital deformities (PKD1, SON, SALL1, BMPR1B, ITGA8), which are partially overlapping with our patients’ phenotypes. We further identified eight incidental findings in seven genes related to Mendelian syndromes without known association with reproductive anomalies (TEK, COL11A1, ANKRD11, LEMD3, DLG5, SPTB, BMP2), which represent potential phenotype expansions of these genes.

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Acknowledgements

We appreciate all of the patients, their families, and clinical research coordinators who participated in this project. We thank GeneSeeq Inc. for exome sequencing technical support. We thank Beijing Ekitech Co. Ltd. for the support in bioinformatics analyses.

Funding

This research was funded in part by the National Natural Science Foundation of China (81822030 and 82072391 to N.W., 81930068 and 81772299 to Z.W., 81972132 to G.Q., 81972037 to J.Z., and 81830043 to Z.L.), National Science Foundation for Youth grant no. 81801401 (to C.N.), Beijing Natural Science Foundation (JQ20032 to N.W. and 7191007 to Z.W.), Capital’s Funds for Health Improvement and Research (2020-4-40114 to N.W.), Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program, CAMS Innovation Fund for Medical Sciences (CIFMS, 2020-I2M-C&T-B-030 to J.Z., 2020-I2M-C&T-A-015 to Y.M., and CAMS-2017-I2M-1-002 to L.Z.), and Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2019PT320025).

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Author notes

  1. These authors contributed equally: Weijie Tian, Na Chen.

  2. These authors jointly supervised this work: Nan Wu, Lan Zhu.

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

    Weijie Tian, Na Chen, Yang Ye, Congcong Ma, Ze Liang, Shuang Song, Yuan Wang, Jiali Duan & Lan Zhu

  2. Department of Obstetrics and Gynaecology, the 3rd Affiliated Hospital of Shenzhen University, Luohu Hospital, Shenzhen, Guangdong, 518000, China

    Chenglu Qin

  3. Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, 100730, China

    Yuchen Niu, L. Xiaoxin, Lina Zhao, Hengqiang Zhao, Zefu Chen, Jiachen Lin, Zihui Yan, Sen Zhao, Terry Jianguo Zhang, Guixing Qiu, Zhihong Wu & Nan Wu

  4. Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Yuchen Niu, L. Xiaoxin, Lina Zhao & Zhihong Wu

  5. Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

    Hengqiang Zhao, Zefu Chen, Jiachen Lin, Zihui Yan, Sen Zhao, Terry Jianguo Zhang, Guixing Qiu & Nan Wu

  6. Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing, China

    Zhihong Wu & Nan Wu

Authors
  1. Weijie Tian
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  2. Na Chen
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Contributions

Conceptualization: N.W. and L.Z. Cohort enrollment: N.C., W.T., H.P., C.M., Z.L., S.S., Y.Y., Y.N., X.L., L.Z., Z.C., J.L., and J.D. Funding acquisition: N.W., Z.L., J.Z., G.Q., and Z.W. Genetic data analysis: S.Z. and N.W. Bioinformatics analysis: S.Z. and H.Z. Writing - review & editing: N.W. and L.Z. Writing original draft: W.T., S.Z., N.C., L.Z., and N.W. All authors provided crucial input on several iterations of the manuscript, and all authors have approved the final version.

Corresponding authors

Correspondence to Nan Wu or Lan Zhu.

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The authors declare no competing interests.

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Approval for the study was obtained from the ethics committee at Peking Union Medical College Hospital (ZS-1858, S-452).

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Tian, W., Chen, N., Ye, Y. et al. A genotype-first analysis in a cohort of Mullerian anomaly. J Hum Genet 67, 347–352 (2022). https://doi.org/10.1038/s10038-021-00996-w

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