Abstract
Research question
Asthenoteratospermia is characterized by malformed spermatozoa with motility defects,
which results in male infertility. Multiple morphological abnormalities of the sperm
flagella (MMAF) is a hallmark of asthenoteratospermia. The genetic causes of MMAF,
however, are unknown in about one-third of cases. Which other MMAF-associated genes
are waiting to be discovered?
Design
Whole-exome sequencing was conducted to identify causative genes in a man with MMAF.
Immunofluorescence staining and western blot were applied to assess the pathogenicity
of the identified variant. Intracytoplasmic sperm injection (ICSI) was used to assist
fertilization for the patient with MMAF.
Result
Sanger sequencing of the family demonstrated that the infertile man carried a homozygous
DNAH17 variant (c. 4810C>T [p.R1604C]). The obviously decreased DNAH17 expression was observed
in HEK293T cells transfected with MUT-DNAH17 plasmid compared with cells with WT-DNAH17 plasmid. Immunofluorescence analysis showed that this mutation induced significant
decrease in DNAH17 expression, which negatively affected the DNAH8 expression in the
patient's spermatozoa. Moreover, the outcome of ICSI in the patient was unsuccessful.
Conclusion
Our study revealed a novel homozygous missense mutation in DNAH17 involved in MMAF phenotype. The finding of the novel mutation in DNAH17 enriches the gene variant spectrum of MMAF, further contributing to diagnosis, genetic
counselling and prognosis for male infertility.
KEYWORDS
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Biography
Rui Zheng is a PhD candidate at the Department of Obstetrics and Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases. Her main research topic is the pathogenesis of male infertility.
Article info
Publication history
Published online: May 21, 2021
Accepted:
May 8,
2021
Received in revised form:
April 14,
2021
Received:
November 9,
2020
Declaration: The authors report no financial or commercial conflicts of interest.Identification
Copyright
© 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
