title: [Human infertility: meiotic genes as potential candidates].
abstract: Up to now, the identification of gene mutations causing infertility in humans remains poorly investigated. Temporal progression through meiosis and meiosis specific genes had been extensively characterized in yeast. Recently some mammalian homologous were found. The molecular mechanisms regulating entry into and progression through meiosis in mammals are still unknown. However, disruption of some meiotic genes in mouse showed an essential role of them in meiotic chromosome synapsis and gametogenesis. Moreover, the phenotype of gonads in null mutant mice for some meiotic genes (failure to initiate or blockage in meiosis, lack of gametes or small size of gonads...) could be strikingly similar to clinical observations found in human infertility. The aim of this study was to identify putative mutations in 5 meiotic genes of several clinically well-characterized patients who present unexplained infertility (normal karyotype, women with premature ovarian failure, men with azospermia and without Y micro-deletion). For this purpose, the exons of these 5 genes (DMC1, SPO11, MSH4, MSH5, CCNA1) were all amplified by PCR with specific primers and each amplified-exon was sequenced. Sequences were aligned in comparison to the human corresponding gene available in Genbank. Many heterozygous mutations were found in different genes. Two homozygous mutations were found in MSH4 and DMC1 genes in a young man presenting a testis vanishing syndrome and a woman presenting a premature ovarian failure, respectively. Consequences of such mutations will be examined and verified in model organisms (yeast, mouse) to check the relevance of the mutations in clinical setting.
authors.affiliation: Inra, laboratoire de biologie du développement et biotechnologies, bâtiment J. Poly, 78350 Jouy en Josas, France. pepin@jouy.inra.fr
authors.forename: B
authors.initials: B
authors.lastname: Mandon-Pépin
authors.forename: C
authors.initials: C
authors.lastname: Derbois
authors.forename: F
authors.initials: F
authors.lastname: Matsuda
authors.forename: C
authors.initials: C
authors.lastname: Cotinot
authors.forename: D J
authors.initials: DJ
authors.lastname: Wolgemuth
authors.forename: K
authors.initials: K
authors.lastname: Smith
authors.forename: K
authors.initials: K
authors.lastname: McElreavey
authors.forename: A
authors.initials: A
authors.lastname: Nicolas
authors.forename: M
authors.initials: M
authors.lastname: Fellous
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D018797:Cell Cycle Proteins; D019925:Cyclin A / Q000235:genetics; D056750:Cyclin A1; D004268:DNA-Binding Proteins / Q000235:genetics; D004706:Endodeoxyribonucleases; D004950:Esterases / Q000235:genetics; D005260:Female; D006801:Humans; D007246:Infertility / Q000235:genetics*; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins; D028044:Phosphate-Binding Proteins; D011506:Proteins / Q000235:genetics; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D019925:Cyclin A; D056750:Cyclin A1; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D004950:Esterases; D009687:Nuclear Proteins; D028044:Phosphate-Binding Proteins; D011506:Proteins; D000099257:Meiotic Recombination Protein SPO11; C503745:CCNA1 protein, human; C503747:Ccna1 protein, mouse; C513032:Dmc1 protein, mouse; C409221:MSH4 protein, human; C118481:MSH5 protein, human; C502328:Msh4 protein, mouse; C512847:Msh5 protein, mouse; C074556:DMC1 protein, human