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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

dc.contributor.authorLORÈS, Patrick
dc.contributor.authorCOUTTON, Charles
dc.contributor.authorEL KHOURI, Elma
dc.contributor.authorSTOUVENEL, Laurence
dc.contributor.authorGIVELET, Maelle
dc.contributor.authorTHOMAS, Lucie
dc.contributor.authorRODE, Baptiste
dc.contributor.authorSCHMITT, Alain
dc.contributor.authorLOUIS, Bruno
dc.contributor.authorSAKHELI, Zeinab
dc.contributor.authorCHAUDHRY, Marhaba
dc.contributor.authorFERNANDEZ-GONZALES, Angeles
dc.contributor.authorMITSIALIS, Alex
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorDACHEUX, Denis
dc.contributor.authorWOLF, Jean-Philippe
dc.contributor.authorPAPON, Jean-François
dc.contributor.authorGACON, Gérard
dc.contributor.authorESCUDIER, Estelle
dc.contributor.authorARNOULT, Christophe
dc.contributor.authorBONHIVERS, Mélanie
dc.contributor.authorSAVINOV, Sergey
dc.contributor.authorAMSELEM, Serge
dc.contributor.authorRAY, Pierre
dc.contributor.authorDULIOUST, Emmanuel
dc.contributor.authorTOURÉ, Aminata
dc.date.accessioned2023-06-26T08:14:53Z
dc.date.available2023-06-26T08:14:53Z
dc.date.issued2018-04-01
dc.identifier.issn0964-6906
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182813
dc.description.abstractEnMotile cilia and sperm flagella share an extremely conserved microtubule-based cytoskeleton, called the axoneme, which sustains beating and motility of both organelles. Ultra-structural and/or functional defects of this axoneme are well-known to cause primary ciliary dyskinesia (PCD), a disorder characterized by recurrent respiratory tract infections, chronic otitis media, situs inversus, male infertility and in most severe cases, hydrocephalus. Only recently, mutations in genes encoding axonemal proteins with preferential expression in the testis were identified in isolated male infertility; in those cases, individuals displayed severe asthenozoospermia due to Multiple Morphological Abnormalities of the sperm Flagella (MMAF) but not PCD features. In this study, we performed genetic investigation of two siblings presenting MMAF without any respiratory PCD features, and we report the identification of the c.2018T > G (p.Leu673Pro) transversion in AK7, encoding an adenylate kinase, expressed in ciliated tissues and testis. By performing transcript and protein analyses of biological samples from individual carrying the transversion, we demonstrate that this mutation leads to the loss of AK7 protein in sperm cells but not in respiratory ciliated cells, although both cell types carry the mutated transcript and no tissue-specific isoforms were detected. This work therefore, supports the notion that proteins shared by both cilia and sperm flagella may have specific properties and/or function in each organelle, in line with the differences in their mode of assembly and organization. Overall, this work identifies a novel genetic cause of asthenozoospermia due to MMAF and suggests that in humans, more deleterious mutations of AK7 might induce PCD.
dc.language.isoen
dc.publisherOxford University Press (OUP)
dc.title.enHomozygous 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
dc.typeArticle de revueen_US
dc.identifier.doi10.1093/hmg/ddy034
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie moléculaire
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biophysique
dc.subject.halSciences du Vivant [q-bio]/Biologie cellulaire/Organisation et fonctions cellulaires [q-bio.SC]
dc.subject.halSciences du Vivant [q-bio]/Biologie cellulaire/Interactions cellulaires [q-bio.CB]
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologie/Parasitologie
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologie/Protistologie
bordeaux.journalHuman Molecular Geneticsen_US
bordeaux.page1196-1211
bordeaux.volume27
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue7
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
bordeaux.import.sourcehal
hal.identifierhal-02346745
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Human%20Molecular%20Genetics&rft.date=2018-04-01&rft.volume=27&rft.issue=7&rft.spage=1196-1211&rft.epage=1196-1211&rft.eissn=0964-6906&rft.issn=0964-6906&rft.au=LOR%C3%88S,%20Patrick&COUTTON,%20Charles&EL%20KHOURI,%20Elma&STOUVENEL,%20Laurence&GIVELET,%20Maelle&rft.genre=article


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