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Detection of heterozygous mutation in hook microtubule-tethering protein 1 in three patients with decapitated and decaudated spermatozoa syndrome
  1. Huixing Chen1,2,
  2. Yong Zhu3,
  3. Zijue Zhu2,
  4. Erlei Zhi2,
  5. Keming Lu3,
  6. Xiaobo Wang3,
  7. Feng Liu1,2,3,
  8. Zheng Li1,2,3,
  9. Weiliang Xia1
  1. 1School of Biomedical Engineering, Shanghai Jiao Tong University, Med-X Research Institute, Shanghai, China
  2. 2Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  3. 3Shanghai Human Sperm Bank, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  1. Correspondence to Zheng Li; lizhengboshi{at}163.com and Professor Weiliang Xia, School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China; wlxia{at}sjtu.edu.cn

Abstract

Background The mechanism of intramanchette transport is crucial to the transformation of sperm tail and the nuclear condensation during spermiogenesis. Although few dysfunctional proteins could result in abnormal junction between the head and tail of spermatozoon, little is known about the genetic cues in this process.

Objective Based on patients with severe decapitated and decaudated spermatozoa (DDS) syndrome, the study aimed to validate whether new mutation exists on their Hook microtubule-tethering protein 1 (HOOK1) genes and follow their results of assisted reproduction treatment (ART).

Methods 7 severe teratozoospermia patients with DDS (proportion >95%) and three relative members in one pedigree were collected to sequence the whole genomic DNA. The fertilisation rates (FRs) of these patients were followed. Morphological observation and interspecies intracytoplasmic sperm injection (ICSI) assays were applied.

Results A novel missense mutation of A to G (p.Q286R) in patients with DDS (n=3/7) was found in the HOOK1 gene, which was inherited from the mother in one patient. This variant was absent in 160 fertile population-matched control individuals. Morphological observation showed that almost all the DDS broke into decaudated heads and headless tails at the implantation fossa or the basal plate. The clinical studies indicated that the mutation might cause reduced FRs on both ART (FR=18.07%) and interspecies ICSI (FR=16.98%).

Conclusions An unreported mutation in HOOK1 gene was identified, which might be responsible to some patients with DDS. Further studies need to uncover the molecular mechanism of spermiogenesis for genomic therapy.

  • Decapitated and decaudated spermatozoa
  • Severe teratozoospermia
  • HOOK1
  • Spermiogenesis
  • Mutation

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Footnotes

  • Contributors The experiments were designed by WX, ZL, HC, YZ; the experiments were performed by HC, YZ, ZZ, EZ, KL and XW; the data were analysed by YZ, FL and ZZ; and the paper was written by HC, YZ and WX.

  • Funding This study was supported by grants from Ministry of Science and Technology of China (2012CB966603, 2015AA020404) and the National Natural Science Foundation of China (31270032,81773115).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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