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Novel compound heterozygous DNAAF2 mutations cause primary ciliary dyskinesia in a Han Chinese family

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

Abstract

Purpose

Primary ciliary dyskinesia (PCD), which commonly causes male infertility, is an inherited autosomal recessive disorder. This study aimed to investigate the clinical manifestations and screen mutations associated with the dynein axonemal assembly factor 2 (DNAAF2) gene in a Han Chinese family with PCD.

Methods

A three-generation family with PCD was recruited in this study. Eight family members underwent comprehensive medical examinations. Genomic DNA was extracted from the participants’ peripheral blood, and targeted next-generation sequencing technology was used to perform the mutation screening. The DNAAF2 expression was analyzed by immunostaining and Western blot.

Results

The proband exhibited the typical clinical features of PCD. Spermatozoa from the proband showed complete immotility but relatively high viability. Two novel compound heterozygous mutations in the DNAAF2 gene, c.C156A [p.Y52X] and c.C26A [p.S9X], were identified. Both nonsense mutations were detected in the proband, whereas the other unaffected family members carried either none or only one of the two mutations. The two nonsense heterozygous mutations were not detected in the 600 ethnically matched normal controls or in the Genome Aggregation Database. The defect of the DNAAF2 and the outer dynein arms and inner dynein arms were notably observed in the spermatozoa from the proband by immunostaining.

Conclusion

This study identified two novel compound heterozygous mutations of DNAAF2 leading to male infertility as a result of PCD in a Han Chinese family. The findings may enhance the understanding of the pathogenesis of PCD and improve reproductive genetic counseling in China.

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Author notes

  1. Minghan Sun and Yi Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Genetics and Division of Human Morbid Genomics, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China

    Minghan Sun, Hao Tan & Yongxin Ma

  2. Central of Reproductive Medicine, Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, 32 Road West 2, the First Ring, Chengdu, 640072, Sichuan, China

    Minghan Sun, Yi Wang, Hailian Wang, Tiantian Lei, Xiaojie Li, Xiaojian Zhang, Wen Xiong & Ke Dou

  3. The Key Laboratory for Human Disease Gene Study of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China

    Yi Zhang &  JiyunYang

Authors
  1. Minghan Sun
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  2. Yi Zhang
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Correspondence to Ke Dou or Yongxin Ma.

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Sun, M., Zhang, Y., JiyunYang et al. Novel compound heterozygous DNAAF2 mutations cause primary ciliary dyskinesia in a Han Chinese family. J Assist Reprod Genet 37, 2159–2170 (2020). https://doi.org/10.1007/s10815-020-01859-7

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  • DOI: https://doi.org/10.1007/s10815-020-01859-7

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