DNAH17 is associated with asthenozoospermia and multiple morphological abnormalities of sperm flagella.
DNAH17
MMAF
asthenozoospermia
biallelic mutations
Journal
Annals of human genetics
ISSN: 1469-1809
Titre abrégé: Ann Hum Genet
Pays: England
ID NLM: 0416661
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
06
05
2019
revised:
05
11
2019
accepted:
05
11
2019
pubmed:
17
12
2019
medline:
24
3
2021
entrez:
17
12
2019
Statut:
ppublish
Résumé
Multiple morphological abnormalities of the sperm flagella (MMAF) is one kind of severe asthenozoospermia, which is caused by dysplastic development of sperm flagella. In our study, we sought to investigate the novel gene mutations leading to severe asthenozoospermia and MMAF. The patient's spermatozoa were tested by Papanicolaou staining and transmission electron microscopy. Whole exome sequencing was performed on the patient with severe asthenozoospermia and MMAF. Sanger sequencing verified the mutations in the family. The expression of DNAH17 was detected by immunofluorescence and Western blot. Spermatozoa sample from the patient showed severe asthenozoospermia and MMAF. We detected biallelic mutations (c.C4445T, p.A1482V and c.C6857T, and p.S2286L) in DNAH17 (MIM:610063). The protein expression of DNAH17 was almost undetectable in spermatozoa from the patient with the biallelic mutations. These results demonstrated that DNAH17 may be involved in severe asthenozoospermia and MMAF.
Sections du résumé
BACKGROUND
Multiple morphological abnormalities of the sperm flagella (MMAF) is one kind of severe asthenozoospermia, which is caused by dysplastic development of sperm flagella. In our study, we sought to investigate the novel gene mutations leading to severe asthenozoospermia and MMAF.
METHODS AND MATERIALS
The patient's spermatozoa were tested by Papanicolaou staining and transmission electron microscopy. Whole exome sequencing was performed on the patient with severe asthenozoospermia and MMAF. Sanger sequencing verified the mutations in the family. The expression of DNAH17 was detected by immunofluorescence and Western blot.
RESULTS
Spermatozoa sample from the patient showed severe asthenozoospermia and MMAF. We detected biallelic mutations (c.C4445T, p.A1482V and c.C6857T, and p.S2286L) in DNAH17 (MIM:610063). The protein expression of DNAH17 was almost undetectable in spermatozoa from the patient with the biallelic mutations.
CONCLUSION
These results demonstrated that DNAH17 may be involved in severe asthenozoospermia and MMAF.
Substances chimiques
DNAH17 protein, human
EC 3.6.1.-
Axonemal Dyneins
EC 3.6.4.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
271-279Informations de copyright
© 2019 John Wiley & Sons Ltd/University College London.
Références
Amiri-Yekta, A., Coutton, C., Kherraf, Z. E., Karaouzene, T., Le Tanno, P., Sanati, M. H., … Ray, P. F. (2016). Whole-exome sequencing of familial cases of multiple morphological abnormalities of the sperm flagella (MMAF) reveals new DNAH1 mutations. Human Reproduction, 31(12), 2872-2880. Retrieved from https://doi.org/10.1093/humrep/dew262
Ben Khelifa, M., Coutton, C., Zouari, R., Karaouzene, T., Rendu, J., Bidart, M., … Ray, P. F. (2014). Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella. American Journal of Human Genetics, 94(1), 95-104. Retrieved from https://doi.org/10.1016/j.ajhg.2013.11.017
Coutton, C., Vargas, A. S., Amiri-Yekta, A., Kherraf, Z. E., Ben Mustapha, S. F., Le Tanno, P., … Ray, P. F. (2018). Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human. Nature Communications, 9(1), 686. Retrieved from https://doi.org/10.1038/s41467-017-02792-7
Coutton, C., Martinez, G., Kherraf, Z. E., Amiri-Yekta, A., Boguenet, M., Saut, A., … Ray, P. F. (2019). Bi-allelic mutations in ARMC2 lead to severe astheno-teratozoospermia due to sperm flagellum malformations in humans and mice. American Journal of Human Genetics, 104(2), 331-340. Retrieved from https://doi.org/10.1016/j.ajhg.2018.12.013
Dirami, T., Rode, B., Jollivet, M., Da Silva, N., Escalier, D., Gaitch, N., … Toure, A. (2013). Missense mutations in SLC26A8, encoding a sperm-specific activator of CFTR, are associated with human asthenozoospermia. American Journal of Human Genetics, 92(5), 760-766. Retrieved from https://doi.org/10.1016/j.ajhg.2013.03.016
Dong, F. N., Amiri-Yekta, A., Martinez, G., Saut, A., Tek, J., Stouvenel, L., … Coutton, C. (2018). Absence of CFAP69 causes male infertility due to multiple morphological abnormalities of the flagella in human and mouse. American Journal of Human Genetics, 102(4), 636-648. Retrieved from https://doi.org/10.1016/j.ajhg.2018.03.007
Gibbons, I. R. (1995). Dynein family of motor proteins: Present status and future questions. Cell Motility and the Cytoskeleton, 32(2), 136-144. Retrieved from https://doi.org/10.1002/cm.970320214
He, X., Li, W., Wu, H., Lv, M., Liu, W., Liu, C., … Cao, Y. (2019). Novel homozygous CFAP69 mutations in humans and mice cause severe asthenoteratospermia with multiple morphological abnormalities of the sperm flagella. Journal of Medical Genetics, 56(2), 96-103. Retrieved from https://doi.org/10.1136/jmedgenet-2018-105486
Ibanez-Tallon, I., Heintz, N., & Omran, H. (2003). To beat or not to beat: Roles of cilia in development and disease. Human Molecular Genetics, 12(1), R27-R35.
Kherraf, Z. E., Amiri-Yekta, A., Dacheux, D., Karaouzene, T., Coutton, C., Christou-Kent, M., … Ray, P. F. (2018). A homozygous ancestral SVA-insertion-mediated deletion in WDR66 induces multiple morphological abnormalities of the sperm flagellum and male infertility. American Journal of Human Genetics, 103(3), 400-412. Retrieved from https://doi.org/10.1016/j.ajhg.2018.07.014
Li, Y., Yagi, H., Onuoha, E. O., Damerla, R. R., Francis, R., Furutani, Y., … Lo, C. W. (2016). DNAH6 and its interactions with PCD genes in heterotaxy and primary ciliary dyskinesia. Plos Genetics, 12(2), e1005821. Retrieved from https://doi.org/10.1371/journal.pgen.1005821
Li, L., Wang, B., Zhang, W., Chen, B., Luo, M., Wang, J., … Kee, K. (2017). A homozygous NOBOX truncating variant causes defective transcriptional activation and leads to primary ovarian insufficiency. Human Reproduction, 32(1), 248-255. Retrieved from https://doi.org/10.1093/humrep/dew271
Li, L., Sha, Y. W., Xu, X., Mei, L. B., Qiu, P. P., Ji, Z. Y., … Li, P. (2018). DNAH6 is a novel candidate gene associated with sperm head anomaly. Andrologia, Retrieved from https://doi.org/10.1111/and.12953
Li, W., He, X., Yang, S., Liu, C., Wu, H., Liu, W., … Cao, Y. (2019a). Biallelic mutations of CFAP251 cause sperm flagellar defects and human male infertility. Journal of Human Genetics, 64(1), 49-54. Retrieved from https://doi.org/10.1038/s10038-018-0520-1
Li, Y., Sha, Y., Wang, X., Ding, L., Liu, W., Ji, Z., … Lu, Z. (2019b). DNAH2 is a novel candidate gene associated with multiple morphological abnormalities of the sperm flagella. Clinical Genetics, 95, 590-600. Retrieved from https://doi.org/10.1111/cge.13525
Liu, C., Lv, M., He, X., Zhu, Y., Amiri-Yekta, A., Li, W., … Cao, Y. (2019a). Homozygous mutations in SPEF2 induce multiple morphological abnormalities of the sperm flagella and male infertility. Journal of Medical Genetics, Retrieved from https://doi.org/10.1136/jmedgenet-2019-106011
Liu, W., He, X., Yang, S., Zouari, R., Wang, J., Wu, H., … Zhang, F. (2019b). Bi-allelic mutations in TTC21A induce asthenoteratospermia in humans and mice. American Journal of Human Genetics, 104(4), 738-748. Retrieved from https://doi.org/10.1016/j.ajhg.2019.02.020
Liu, W., Sha, Y., Li, Y., Mei, L., Lin, S., Huang, X., … Lu, Z. (2019c). Loss-of-function mutations in SPEF2 cause multiple morphological abnormalities of the sperm flagella (MMAF). Journal of Medical Genetics, 56, 678-684. Retrieved from https://doi.org/10.1136/jmedgenet-2018-105952
Lores, P., Coutton, C., El Khouri, E., Stouvenel, L., Givelet, M., Thomas, L., … Toure, A. (2018). Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia. Human Molecular Genetics, 27(7), 1196-1211. Retrieved from https://doi.org/10.1093/hmg/ddy034
Martinez, G., Kherraf, Z. E., Zouari, R., Fourati Ben Mustapha, S., Saut, A., Pernet-Gallay, K., … Coutton, C. (2018). Whole-exome sequencing identifies mutations in FSIP2 as a recurrent cause of multiple morphological abnormalities of the sperm flagella. Human Reproduction, 33(10), 1973-1984. Retrieved from https://doi.org/10.1093/humrep/dey264
Mazor, M., Alkrinawi, S., Chalifa-Caspi, V., Manor, E., Sheffield, V. C., Aviram, M., & Parvari, R. (2011). Primary ciliary dyskinesia caused by homozygous mutation in DNAL1, encoding dynein light chain 1. American Journal of Human Genetics, 88(5), 599-607. Retrieved from https://doi.org/10.1016/j.ajhg.2011.03.018
Milisav, I., & Affara, N.A. (1998). A potential human axonemal dynein heavy-chain gene maps to 17q25. Mammalian Genome, 9(5), 404-407. https://doi.org/10.1007/s003359900782
Mitchison, H. M., Schmidts, M., Loges, N. T., Freshour, J., Dritsoula, A., Hirst, R. A., … Mitchell, D. R. (2012). Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia. Nature Genetics, 44(4), 381-389, s381-382. Retrieved from https://doi.org/10.1038/ng.1106
Roberts, A. J., Kon, T., Knight, P. J., Sutoh, K., & Burgess, S. A. (2013). Functions and mechanics of dynein motor proteins. Nature Reviews Molecular Cell Biology, 14(11), 713-726. Retrieved from https://doi.org/10.1038/nrm3667
Sha, Y. W., Xu, X., Mei, L. B., Li, P., Su, Z. Y., He, X. Q., & Li, L. (2017). A homozygous CEP135 mutation is associated with multiple morphological abnormalities of the sperm flagella (MMAF). Gene, 633, 48-53. Retrieved from https://doi.org/10.1016/j.gene.2017.08.033
Sha, Y., Liu, W., Wei, X., Zhu, X., Luo, X., Liang, L., & Guo, T. (2019a). Biallelic mutations in sperm flagellum 2 cause human multiple morphological abnormalities of the sperm flagella (MMAF) phenotype. Clinical Genetics, 96, 385-393. Retrieved from https://doi.org/10.1111/cge.13602
Sha, Y. W., Wang, X., Xu, X., Su, Z. Y., Cui, Y., Mei, L. B., … Li, L. (2019b). Novel mutations in CFAP44 and CFAP43 cause multiple morphological abnormalities of the sperm flagella (MMAF). Reproductive Sciences, 26(1), 26-34. Retrieved from https://doi.org/10.1177/1933719117749756
Shen, Y., Zhang, F., Li, F., Jiang, X., Yang, Y., Li, X., … Xu, W. (2019). Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella. Nature Communications, 10(1), 433. Retrieved from https://doi.org/10.1038/s41467-018-08182-x
Tang, S., Wang, X., Li, W., Yang, X., Li, Z., Liu, W., … Zhang, F. (2017). Biallelic mutations in CFAP43 and CFAP44 cause male infertility with multiple morphological abnormalities of the sperm flagella. American Journal of Human Genetics, 100(6), 854-864. Retrieved from https://doi.org/10.1016/j.ajhg.2017.04.012
Viswanadha, R., Sale, W. S., & Porter, M. E. (2017). Ciliary motility: Regulation of axonemal dynein motors. Cold Spring Harbor Perspectives in Biology, 9(8), a018325. Retrieved from https://doi.org/10.1101/cshperspect.a018325
Wang, X., Jin, H., Han, F., Cui, Y., Chen, J., Yang, C., … Gao, Z. (2017). Homozygous DNAH1 frameshift mutation causes multiple morphological anomalies of the sperm flagella in Chinese. Clinical Genetics, 91(2), 313-321. Retrieved from https://doi.org/10.1111/cge.12857
Whitfield, M., Thomas, L., Bequignon, E., Schmitt, A., Stouvenel, L., Montantin, G., … Legendre, M. (2019). Mutations in DNAH17, encoding a sperm-specific axonemal outer dynein arm heavy chain, cause isolated male infertility due to asthenozoospermia. American Journal of Human Genetics, 105(1), 198-212. Retrieved from https://doi.org/10.1016/j.ajhg.2019.04.015
Wu, H., Li, W., He, X., Liu, C., Fang, Y., Zhu, F., … Cao, Y. (2018). Novel CFAP43 andCFAP44 mutations cause male infertility with multiple morphological abnormalities of the sperm flagella (MMAF). Reproductive Biomedicine Online, 38, 769-778. Retrieved from https://doi.org/10.1016/j.rbmo.2018.12.037