Novel mutations in DNAH17 cause sperm flagellum defects and their influence on ICSI outcome
Open accessAbstract
Purpose To identify new mutations in DNAH17 that cause male infertility and analyze intracytoplasmic sperm injection (ICSI) outcomes in patients with DNAH17 mutations. Methods A total of five cases of new DNAH17 mutations exhibiting the multiple morphological abnormalities of the sperm flagella (MMAF) phenotype were identified through semen analysis and genetic testing. They were recruited at our reproductive medicine center from September 2018 to July 2022. Information on DNAH17 genetic mutations and ICSI outcomes was systematically explored following a literature review. Results Three novel compound mutations in DNAH17 were identified in patients with male infertility caused by MMAF. This study and previous publications included 21 patients with DNAH17 mutations. DNAH17 has been associated with asthenozoospermia and male infertility, but different types of DNAH17 variants appear to be involved in different sperm phenotypes. In 11 couples of infertile patients with DNAH17 mutations, there were 17 ICSI cycles and 13 embryo transplantation cycles. Only three men with DNAH17 variants ultimately achieved clinical pregnancy with their partners through ICSI combined with assisted oocyte activation (AOA). Conclusions Loss-of-function mutations in DNAH17 can lead to severe sperm flagellum defects and male infertility. Patients with MMAF-harboring DNAH17 mutations generally have worse pregnancy outcomes following ICSI. ICSI combined with AOA may improve the outcome of assisted reproductive techniques (ARTs) for men with DNAH17 variants.
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Exome sequencing approaches have identified pathogenic variants in more than 40 genes related to the MMAF phenotype.
“In this context, significant advances have been made, particularly exome sequencing approaches that have identified pathogenic variants in more than 40 genes related to the MMAF phenotype [68], see Supporting Information S1.”
From Recommendations for Human Sperm Morphology Assessment in 2025: An Expert Review From the French BLEFCO Group (2026) · cites this paper as [68]
The Introduction (page not available in our copy) links whole-exome sequencing to the identification of numerous MMAF-associated pathogenic genes. It reports more than 30 genes, however, and does not substantiate the citing sentence’s threshold of more than 40. (LLM, conf=0.88)
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- Authors
- Song, B., Yang, T., Shen, Q., Liu, Y., Wang, C., Li, G., Gao, Y., Cao, Y., & He, X.
- Affiliations
- Anhui Medical University (CN)
- First Affiliated Hospital of Anhui Medical University (CN)
- Corresponding author
- Cao, Yunxia
- He, Xiaojin
- Venue
- Journal of Assisted Reproduction and Genetics
- Published
- 2023-08-14
- Volume
- 40
- Issue
- 10
- Pages
- 2485-2492
- ISSN
- 0740-7769 (ISSN-L)
- 1058-0468
- 1573-7330
- PMC
- PMC10504183
- OpenAlex
- W4385792376
- Cited by
- 30
- References
- 23
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 9
- FWCI
- 6.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Assisted Reproduction and Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82101682)
- Anhui Provincial Key Research and Development Plan (202004j07020032)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- male infertility, assisted oocyte activation, loss-of-function mutations, asthenozoospermia, clinical pregnancy rate
- MeSH terms
- Female, Humans, Infertility, Male, Male, Mutation, Pregnancy, Semen, Sperm Tail, Spermatozoa, Sperm Injections, Intracytoplasmic, Axonemal Dyneins
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