| Autor: |
Guillaume, Martinez, Julie, Beurois, Denis, Dacheux, Caroline, Cazin, Marie, Bidart, Zine-Eddine, Kherraf, Derrick R, Robinson, Véronique, Satre, Gerald, Le Gac, Chandran, Ka, Isabelle, Gourlaouen, Yann, Fichou, Graciane, Petre, Emmanuel, Dulioust, Raoudha, Zouari, Nicolas, Thierry-Mieg, Aminata, Touré, Christophe, Arnoult, Mélanie, Bonhivers, Pierre, Ray, Charles, Coutton |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Journal of medical genetics. 57(10) |
| ISSN: |
1468-6244 |
| Popis: |
Multiple morphological abnormalities of the flagella (MMAF) consistently lead to male infertility due to a reduced or absent sperm motility defined as asthenozoospermia. Despite numerous genes recently described to be recurrently associated with MMAF, more than half of the cases analysed remain unresolved, suggesting that many yet uncharacterised gene defects account for this phenotype METHODS: Exome sequencing was performed on 167 infertile men with an MMAF phenotype. Immunostaining and transmission electron microscopy (TEM) in sperm cells from affected individuals were performed to characterise the ultrastructural sperm defects. Gene inactivation using RNA interference (RNAi) was subsequently performed inWe identified six unrelated affected patients carrying a homozygous deleterious variants in MAATS1, a gene encoding CFAP91, a calmodulin-associated and spoke-associated complex (CSC) protein. TEM and immunostaining experiments in sperm cells showed severe central pair complex (CPC) and radial spokes defects. Moreover, we confirmed that the WDR66 protein is a physical and functional partner of CFAP91 into the CSC. Study ofWe showed that CFAP91 is essential for normal sperm flagellum structure and function in human and |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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