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Is a genetic defect in Fkbp6 a common cause of azoospermia in humans?

Abstract

FK506-binding protein 6 (Fkbp6) is a member of a gene family containing a prolyl isomerase/FK506-binding domain and tetratricopeptide protein-protein interaction domains. Recently, the targeted inactivation of Fkbp6 in mice has been observed to result in aspermic males and the absence of normal pachytene spermatocytes. The loss of Fkbp6 results in abnormal pairing and a misalignment of the homologous chromosomes, and in non-homologous partner switches and autosynapsis of the X chromosome cores in meiotic spermatocytes. In this study, we analyzed whether human FKBP6 gene defects might be associated with human azoospermia. We performed a mutation analysis in all the coding regions of the human FKBP6 gene in 19 patients with azoospermia resulting from meiotic arrest. The expression of the human FKBP6 gene was specific to the testis, and a novel polymorphism site, 245C → G (Y60X) could be found in exon 3. Our findings suggest that the human FKBP6 gene might be imprinted in the testis based on an analysis using two polymorphism sites.

Abbreviations

AZF:

azoospermia factor

DAZ:

deleted in azoospermia

Fkbp6:

FK506-binding protein 6

RBMY:

RNA-binding motif; Y chromosome

RT-PCR:

reverse transcription-polymerase chain reaction

SC:

synaptonemal complex

USP9Y:

ubiquitin-specific protease 9 gene on the Y

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Correspondence to Toshinobu Miyamato.

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These authors equally contributed to this paper

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Miyamato, T., Sato, H., Yogev, L. et al. Is a genetic defect in Fkbp6 a common cause of azoospermia in humans?. Cell Mol Biol Lett 11, 557–569 (2006). https://doi.org/10.2478/s11658-006-0043-1

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Key words

  • Azoospermia
  • FKBP6
  • Genomic imprinting
  • Meiosis
  • Polymorphism