Biallelic variants in
Abnormalities, Multiple
/ genetics
Animals
Asthenozoospermia
/ genetics
Axoneme
/ genetics
Calcium-Binding Proteins
/ genetics
Carrier Proteins
/ genetics
Homozygote
Humans
Infertility, Male
/ genetics
Male
Mutation
/ genetics
Sperm Motility
/ genetics
Sperm Tail
/ metabolism
Spermatozoa
/ pathology
Trypanosoma
/ genetics
Exome Sequencing
genetics
molecular genetics
reproductive medicine
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
13
12
2019
revised:
25
01
2020
accepted:
27
01
2020
pubmed:
13
3
2020
medline:
9
7
2021
entrez:
13
3
2020
Statut:
ppublish
Résumé
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 in We 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 of We showed that CFAP91 is essential for normal sperm flagellum structure and function in human and
Sections du résumé
BACKGROUND
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 in
RESULTS
We 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 of
CONCLUSIONS
We showed that CFAP91 is essential for normal sperm flagellum structure and function in human and
Identifiants
pubmed: 32161152
pii: jmedgenet-2019-106775
doi: 10.1136/jmedgenet-2019-106775
doi:
Substances chimiques
CFAP91 protein, human
0
Calcium-Binding Proteins
0
Carrier Proteins
0
WDR66 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
708-716Informations de copyright
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.