Male Infertility Database

Search Results

PMID	31735292
Gene Name	TTC29
Condition	Morphological abnormalities of the sperm flagellum (MMAF), Asthenozoospermia and Male Infertility
Association	Associated
Mutation	c.1761 � G>A, c.330_334delGGAGG, c.750C>A
Population size	167
Population details	167 men affected by primary infertility associated with a MMAF
Sex	Male
Infertility type	Male infertility
Associated genes	NGS
Mutations in TTC29, Encoding an Evolutionarily Conserved Axonemal Protein, Result in Asthenozoospermia and Male Infertility Lor�s P, Dacheux D, Kherraf ZE, Nsota Mbango JF, Coutton C, Stouvenel L, Ialy-Radio C, Amiri-Yekta A, Whitfield M, Schmitt A, Cazin C, Givelet M, Ferreux L, Fourati Ben Mustapha S, Halouani L, Marrakchi O, Daneshipour A, El Khouri E, Do Cruzeiro M, Favier M, Guillonneau F, Chaudhry M, Sakheli Z, Wolf JP, Patrat C, Gacon G, Savinov SN, Hosseini SH, Robinson DR, Zouari R, Ziyyat A, Arnoult C, Dulioust E, Bonhivers M, Ray PF, Tour� A. In humans, structural or functional defects of the sperm flagellum induce asthenozoospermia, which accounts for the main sperm defect encountered in infertile men. Herein we focused on morphological abnormalities of the sperm flagellum (MMAF), a phenotype also termed "short tails," which constitutes one of the most severe sperm morphological defects resulting in asthenozoospermia. In previous work based on whole-exome sequencing of a cohort of 167 MMAF-affected individuals, we identified bi-allelic loss-of-function mutations in more than 30% of the tested subjects. In this study, we further analyzed this cohort and identified five individuals with homozygous truncating variants in TTC29, a gene preferentially and highly expressed in the testis, and encoding a tetratricopeptide repeat-containing protein related to the intraflagellar transport (IFT). One individual carried a frameshift variant, another one carried a homozygous stop-gain variant, and three carried the same splicing variant affecting a consensus donor site. The deleterious effect of this last variant was confirmed on the corresponding transcript and protein product. In addition, we produced and analyzed TTC29 loss-of-function models in the flagellated protist T. brucei and in M. musculus. Both models confirmed the importance of TTC29 for flagellar beating. We showed that in T. brucei the TPR structural motifs, highly conserved between the studied orthologs, are critical for TTC29 axonemal localization and flagellar beating. Overall our work demonstrates that TTC29 is a conserved axonemal protein required for flagellar structure and beating and that TTC29 mutations are a cause of male sterility due to MMAF. CI - Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. FAU - Lorès, Patrick AU - Lorès P AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Dacheux, Denis AU - Dacheux D AD - Université de Bordeaux, Microbiologie Fondamentale et Pathogénicité, CNRS UMR 5234, Bordeaux, France; Institut Polytechnique de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR-CNRS 5234, 33000 Bordeaux, France. FAU - Kherraf, Zine-Eddine AU - Kherraf ZE AD - INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France; CHU de Grenoble, UM GI-DPI, Grenoble 38000, France. FAU - Nsota Mbango, Jean-Fabrice AU - Nsota Mbango JF AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Coutton, Charles AU - Coutton C AD - INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France; CHU Grenoble Alpes, UM de Génétique Chromosomique, Grenoble, France. FAU - Stouvenel, Laurence AU - Stouvenel L AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Ialy-Radio, Come AU - Ialy-Radio C AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Amiri-Yekta, Amir AU - Amiri-Yekta A AD - Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. FAU - Whitfield, Marjorie AU - Whitfield M AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Schmitt, Alain AU - Schmitt A AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Cazin, Caroline AU - Cazin C AD - INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France. FAU - Givelet, Maëlle AU - Givelet M AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Ferreux, Lucile AU - Ferreux L AD - Laboratoire d'Histologie Embryologie - Biologie de la Reproduction - CECOS Groupe Hospitalier Universitaire Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris 75014, France. FAU - Fourati Ben Mustapha, Selima AU - Fourati Ben Mustapha S AD - Histologie Embryologie et Biologie de la Reproduction, Centre de Promotion des Sciences de la Reproduction, Polyclinique les Jasmins, Centre Urbain Nord, 1003 Tunis, Tunisia. FAU - Halouani, Lazhar AU - Halouani L AD - Histologie Embryologie et Biologie de la Reproduction, Centre de Promotion des Sciences de la Reproduction, Polyclinique les Jasmins, Centre Urbain Nord, 1003 Tunis, Tunisia. FAU - Marrakchi, Ouafi AU - Marrakchi O AD - Histologie Embryologie et Biologie de la Reproduction, Centre de Promotion des Sciences de la Reproduction, Polyclinique les Jasmins, Centre Urbain Nord, 1003 Tunis, Tunisia. FAU - Daneshipour, Abbas AU - Daneshipour A AD - Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. FAU - El Khouri, Elma AU - El Khouri E AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Do Cruzeiro, Marcio AU - Do Cruzeiro M AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Favier, Maryline AU - Favier M AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Guillonneau, François AU - Guillonneau F AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Chaudhry, Marhaba AU - Chaudhry M AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Sakheli, Zeinab AU - Sakheli Z AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Wolf, Jean-Philippe AU - Wolf JP AD - INSERM U1016, Institut Cochin, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France; Laboratoire d'Histologie Embryologie - Biologie de la Reproduction - CECOS Groupe Hospitalier Universitaire Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris 75014, France. FAU - Patrat, Catherine AU - Patrat C AD - INSERM U1016, Institut Cochin, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France; Laboratoire d'Histologie Embryologie - Biologie de la Reproduction - CECOS Groupe Hospitalier Universitaire Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris 75014, France. FAU - Gacon, Gérard AU - Gacon G AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France. FAU - Savinov, Sergey N AU - Savinov SN AD - Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA. FAU - Hosseini, Seyedeh Hanieh AU - Hosseini SH AD - Department of Andrology, Reproductive Biomedicine Research Center, Royan Institutefor Reproductive Biomedicine, ACECR, Tehran, Iran. FAU - Robinson, Derrick R AU - Robinson DR AD - Université de Bordeaux, Microbiologie Fondamentale et Pathogénicité, CNRS UMR 5234, Bordeaux, France. FAU - Zouari, Raoudha AU - Zouari R AD - Histologie Embryologie et Biologie de la Reproduction, Centre de Promotion des Sciences de la Reproduction, Polyclinique les Jasmins, Centre Urbain Nord, 1003 Tunis, Tunisia. FAU - Ziyyat, Ahmed AU - Ziyyat A AD - INSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France; Laboratoire d'Histologie Embryologie - Biologie de la Reproduction - CECOS Groupe Hospitalier Universitaire Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris 75014, France. FAU - Arnoult, Christophe AU - Arnoult C AD - INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France. FAU - Dulioust, Emmanuel AU - Dulioust E AD - INSERM U1016, Institut Cochin, Paris 75014, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France; Laboratoire d'Histologie Embryologie - Biologie de la Reproduction - CECOS Groupe Hospitalier Universitaire Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris 75014, France. FAU - Bonhivers, Mélanie AU - Bonhivers M AD - Université de Bordeaux, Microbiologie Fondamentale et Pathogénicité, CNRS UMR 5234, Bordeaux, France. FAU - Ray, Pierre F AU - Ray PF AD - INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France; CHU de Grenoble, UM GI-DPI, Grenoble 38000, France.