Abstract
Premature ovarian failure (POF) is a disorder characterized by amenorrhea and elevated serum gonadotropins before 40 years of age. As X chromosomal abnormalities are often recognized in POF patients, defects of X-linked gene may contribute to POF. Four cases of POF with t(X;autosome) were genetically analyzed. All the translocation breakpoints were determined at the nucleotide level. Interestingly, COL4A6 at Xq22.3 encoding collagen type IV alpha 6 was disrupted by the translocation in one case, but in the remaining three cases, breakpoints did not involve any X-linked genes. According to the breakpoint sequences, two translocations had microhomology of a few nucleotides and the other two showed insertion of 3–8 nucleotides with unknown origin, suggesting that non-homologous end-joining is related to the formation of all the translocations.
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References
Coulam, C. B., Adamson, S. C. & Annegers, J. F. Incidence of premature ovarian failure. Obstet. Gynecol. 67, 604–606 (1986).
Therman, E., Laxova, R. & Susman, B. The critical region on the human Xq. Hum. Genet. 85, 455–461 (1990).
Schlessinger, D., Herrera, L., Crisponi, L., Mumm, S., Percesepe, A., Pellegrini, M. et al. Genes and translocations involved in POF. Am. J. Med. Genet. 111, 328–333 (2002).
Rizzolio, F., Bione, S., Sala, C., Goegan, M., Gentile, M., Gregato, G. et al. Chromosomal rearrangements in Xq and premature ovarian failure: mapping of 25 new cases and review of the literature. Hum. Reprod. 21, 1477–1483 (2006).
Sala, C., Arrigo, G., Torri, G., Martinazzi, F., Riva, P., Larizza, L. et al. Eleven X chromosome breakpoints associated with premature ovarian failure (POF) map to a 15-Mb YAC contig spanning Xq21. Genomics 40, 123–131 (1997).
Rizzolio, F., Sala, C., Alboresi, S., Bione, S., Gilli, S., Goegan, M. et al. Epigenetic control of the critical region for premature ovarian failure on autosomal genes translocated to the X chromosome: a hypothesis. Hum. Genet. 121, 441–450 (2007).
Bano, G., Mansour, S. & Nussey, S. The association of primary hyperparathyroidism and primary ovarian failure: a de novo t(X; 2) (q22p13) reciprocal translocation. Eur. J. Endocrinol. 158, 261–263 (2008).
Allen, R. C., Zoghbi, H. Y., Moseley, A. B., Rosenblatt, H. M. & Belmont, J. W. Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Am J Hum. Genet. 51, 1229–1239 (1992).
Carrel, L. & Willard, H. F. An assay for X inactivation based on differential methylation at the fragile X locus, FMR1. Am. J. Med. Genet. 64, 27–30 (1996).
Kubota, T., Nonoyama, S., Tonoki, H., Masuno, M., Imaizumi, K., Kojima, M. et al. A new assay for the analysis of X-chromosome inactivation based on methylation-specific PCR. Hum. Genet. 104, 49–55 (1999).
Khoshnoodi, J., Pedchenko, V. & Hudson, B. G. Mammalian collagen IV. Microsc. Res. Technol. 71, 357–370 (2008).
Borza, D. B., Bondar, O., Ninomiya, Y., Sado, Y., Naito, I., Todd, P. et al. The NC1 domain of collagen IV encodes a novel network composed of the alpha 1, alpha 2, alpha 5, and alpha 6 chains in smooth muscle basement membranes. J. Biol. Chem. 276, 28532–28540 (2001).
Zhou, J., Ding, M., Zhao, Z. & Reeders, S. T. Complete primary structure of the sixth chain of human basement membrane collagen, alpha 6(IV). Isolation of the cDNAs for alpha 6(IV) and comparison with five other type IV collagen chains. J. Biol. Chem. 269, 13193–13199 (1994).
Sugimoto, K., Yanagida, H., Yagi, K., Kuwajima, H., Okada, M. & Takemura, T. A Japanese family with Alport syndrome associated with esophageal leiomyomatosis: genetic analysis of COL4A5 to COL4A6 and immunostaining for type IV collagen subtypes. Clin. Nephrol. 64, 144–150 (2005).
Hertz, J. M., Juncker, I. & Marcussen, N. MLPA and cDNA analysis improves COL4A5 mutation detection in X-linked Alport syndrome. Clin. Genet. 74, 522–530 (2008).
Mazaud Guittot, S., Verot, A., Odet, F., Chauvin, M. A. & le Magueresse-Battistoni, B. A comprehensive survey of the laminins and collagens type IV expressed in mouse Leydig cells and their regulation by LH/hCG. Reproduction 135, 479–488 (2008).
Prueitt, R. L., Ross, J. L. & Zinn, A. R. Physical mapping of nine Xq translocation breakpoints and identification of XPNPEP2 as a premature ovarian failure candidate gene. Cytogenet. Cell Genet. 89, 44–50 (2000).
Prueitt, R. L., Chen, H., Barnes, R. I. & Zinn, A. R. Most X;autosome translocations associated with premature ovarian failure do not interrupt X-linked genes. Cytogenet. Genome Res. 97, 32–38 (2002).
Lorda-Sanchez, I. J., Ibanez, A. J., Sanz, R. J., Trujillo, M. J., Anabitarte, M. E., Querejeta, M. E. et al. Choroideremia, sensorineural deafness, and primary ovarian failure in a woman with a balanced X-4 translocation. Ophthalmic Genet. 21, 185–189 (2000).
Vizioli, M. G., Sensi, M., Miranda, C., Cleris, L., Formelli, F., Anania, M. C. et al. IGFBP7: an oncosuppressor gene in thyroid carcinogenesis. Oncogene 29, 3835–3844 (2010).
Yen, H. W., Jakimiuk, A. J., Munir, I. & Magoffin, D. A. Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries. Mol. Hum. Reprod. 10, 473–479 (2004).
Tamura, K., Matsushita, M., Endo, A., Kutsukake, M. & Kogo, H. Effect of insulin-like growth factor-binding protein 7 on steroidogenesis in granulosa cells derived from equine chorionic gonadotropin-primed immature rat ovaries. Biol. Reprod. 77, 485–491 (2007).
Gu, W., Zhang, F. & Lupski, J. R. Mechanisms for human genomic rearrangements. Pathogenetics 1, 4 (2008).
Acknowledgements
This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (NM), the Japan Science and Technology Agency (NM), the Ministry of Health, Labour and Welfare, Japan (NM) and Japan Society for the Promotion of Science (JSPS) (NM and AN). AN is a JSPS fellow.
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Nishimura-Tadaki, A., Wada, T., Bano, G. et al. Breakpoint determination of X;autosome balanced translocations in four patients with premature ovarian failure. J Hum Genet 56, 156–160 (2011). https://doi.org/10.1038/jhg.2010.155
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DOI: https://doi.org/10.1038/jhg.2010.155
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