title: A rare synaptonemal complex protein 3 gene variant in unexplained female infertility.
abstract: Synaptonemal complex protein 3 (SYCP3) plays a critical role in homologous chromosome pairing and recombination in meiosis, and mice deficient in this gene show infertility in males and subfertility in females. The aim of our current study was to determine whether genetic alterations in the SYCP3 gene are associated with female infertility in humans. We examined sequence variations of the SYCP3 gene in genomic DNA from 88 Japanese women with unexplained infertility and 165 samples obtained from a fertile control group. Case-control study using seven tagging single nucleotide polymorphisms revealed no significant association between common SYCP3 variants and unexplained infertility. However, only infertile women were homozygous for the minor allele of a novel rare variant in the coding region, c.666A>G (222Q>Q). The minor allele frequency was significantly higher in the infertile cohort (P< 0.05). This variant is predicted to create a cryptic splice site, although the expression of a mini-gene harboring the variant in HeLa cells or mouse testis did not demonstrate any effects on gene splicing. Our current findings therefore suggest that the c.666A>G variant in the SYCP3 gene might possibly contribute to female infertility in humans, although larger studies are needed to assess the possible effects of SYCP3 gene variation on human female infertility.
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nishiyama
authors.forename: T
authors.initials: T
authors.lastname: Kishi
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Bolor
authors.forename: H
authors.initials: H
authors.lastname: Nishizawa
authors.forename: N
authors.initials: N
authors.lastname: Iwata
authors.forename: Y
authors.initials: Y
authors.lastname: Udagawa
authors.forename: H
authors.initials: H
authors.lastname: Kurahashi
mesh_terms: D000328:Adult; D000818:Animals; D044466:Asian People; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D005260:Female; D014644:Genetic Variation; D006367:HeLa Cells; D006801:Humans; D007247:Infertility, Female / Q000235:genetics*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C490060:SYCP3 protein, human