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Mutational landscape of DNAH1 in Chinese patients with multiple morphological abnormalities of the sperm flagella: cohort study and literature review

  • Genetics
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Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

A Correction to this article was published on 17 June 2021

This article has been updated

Abstract

Purpose

Multiple morphological abnormalities of the sperm flagella (MMAF) are important causes of male infertility. Mutations in DNAH1 are the main causative factors proven so far. We aim to determine the mutational landscape of DNAH1 in Chinese patients with MMAF.

Methods

Forty-one Chinese patients with MMAF were enrolled and underwent a 10-gene next-generation sequencing panel screening.

Results

Only the DNAH1 gene was found to have mutations in 12 of these unrelated individuals (29%). Combining published data from two other cohorts of Chinese men with MMAF, we suggest that p.P3909fs*33, p.R868X, p.Q1518X, p.E3284K, and p.R4096L are hotspot mutations. A polymorphism—rs12163565 (G>A)— showed linkage to p.P3909fs*33, suggesting that this involved a founder effect. Four of the 12 patients with DNAH1 mutations were able to use intracytoplasmic sperm injection with their partners and all were successful in obtaining embryos.

Conclusions

Hotspot mutations were identified for Chinese patients with MMAF. MMAF sub-phenotypes might be associated with different combinations of DNAH1 mutations.

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Acknowledgements

The authors thank all enrolled patients.

Funding

This study was supported by grants from the National Natural Science Foundation of China (81971376), a grant from the Health Commission of Pudong New Area, Shanghai, People’s Republic of China (PW2020D-7), a grant from Shanghai Municipal Health Commission for advanced and suitable technology promotion projects (2019SY056), and Clinical Research Plan of SHDC (No. SHDC2020CR4035).

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Author notes

  1. Wen Yu and Miao An contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. Department of Andrology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China

    Wen Yu, Yang Xu, Qingqiang Gao, Hongxiang Wang & Zhipeng Xu

  2. Department of Urology and Andrology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China

    Miao An & Mujun Lu

  3. NuProbe Company, Shanghai, 200433, China

    Yingying Li & Li Zhang

Authors
  1. Wen Yu
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Correspondence to Hongxiang Wang or Zhipeng Xu.

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Supplementary information

Supplementary Figure S1.

Linkage analysis of the DNAH1 p.P3909fs*33 and rs12163565. Mutant loci p.P3909fs*33 (chr3: 52430998) and rs12163565 (G>A, chr3: 52430526) were in the same allele subjected to cloning and sequencing in patients A5389 and A6254. (PDF 656 kb)

Supplementary Table S1.

The DNAH1 mutation list of 12 diagnosed patients with MMAF. The genomic positions of p.P3909fs*33 and rs12163565 are marked in yellow. (XLSX 85 kb)

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Yu, W., An, M., Xu, Y. et al. Mutational landscape of DNAH1 in Chinese patients with multiple morphological abnormalities of the sperm flagella: cohort study and literature review. J Assist Reprod Genet 38, 2031–2038 (2021). https://doi.org/10.1007/s10815-021-02201-5

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  • DOI: https://doi.org/10.1007/s10815-021-02201-5

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