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Journal of Genetics

, 99:6 | Cite as

Assessment of FMR1 triplet repeats in patients affected with mental retardation, fragile X syndrome and primary ovarian insufficiency

  • Zeinab Salimy
  • Mohammad Taghi AkbariEmail author
  • Faravareh Khordadpoor Deilamani
Research Article
  • 22 Downloads

Abstract

The CGG repeats in the FMR1 gene expand in patients with fragile X syndrome, fragile X-associated tremour/ataxia syndrome and fragile X-associated primary ovarian failure. In this study, the CGG repeats in the FMR1 gene were studied in 449 males and 207 females using traditional polymerase chain reaction and triplet repeat primed PCR methods, also 18 CVS samples (six males and 12 females) were tested for prenatal diagnosis. Further, methylation sensitive multiplexed ligation dependent probe amplification was performed on some samples to confirm the results. Regarding the male patients, 1.1% and 9.7% had premutation (PM) and full mutation (FM) alleles, respectively. Also three (0.66%) male patients were mosaic for PM and FM alleles. Among females, 1.9% were GZ carriers and 5.8% were PM carriers. Prenatal diagnosis resulted in detection of two PM and one FM males as well as one FM carrier female. Our results were in concordance with the previously published results.

Keywords

fragile X syndrome mental retardation gray zone full mutation primary ovarian insufficiency. 

Notes

Acknowledgements

We thank the patients and their families for their collabora-tion. The personnel of Tehran Medical Genetics Laboratory are acknowledged for their help and support. This project was financially supported by Tehran Medical Genetics Laboratory, grant number 90006.

References

  1. Campbell S., Eley S. E., McKechanie A. G. and Stanfield A. C. 2016 Endocrine dysfunction in female fmr1 premutation carriers: characteristics and association with ill health. Genes (Basel) 7.Google Scholar
  2. Dean D. D., Agarwal S., Kapoor D., Singh K. and Vati C. 2018 Molecular characterization of FMR1 gene by TP-PCR in women of reproductive age and women with premature ovarian insufficiency. Mol. Diagn. Ther. 22, 91–100.CrossRefGoogle Scholar
  3. Fernandez-Carvajal I., Lopez Posadas B., Pan R., Raske C., Hagerman P. J. and Tassone F. 2009 Expansion of an FMR1 grey-zone allele to a full mutation in two generations. J. Mol. Diagn. 11, 306–310.CrossRefGoogle Scholar
  4. Gatta V., Gennaro E., Franchi S., Cecconi M., Antonucci I., Tommasi M. et al. 2013 MS-MLPA analysis for FMR1 gene: evaluation in a routine diagnostic setting. BMC Med. Genet. 14, 79.CrossRefGoogle Scholar
  5. Hadi P., Haghani K., Noori-Zadeh A. and Bakhtiyari S. 2018 Prevalence of fragile X syndrome among patients with mental retardation in the west of Iran. Front Biol. 13, 464–468.CrossRefGoogle Scholar
  6. Hantash F. M., Goos D. G., Tsao D., Quan F., Buller-Burckle A., Peng M. et al. 2010 Qualitative assessment of FMR1 (CGG)n triplet repeat status in normal, intermediate, premutation, full mutation, and mosaic carriers in both sexes: implications for fragile X syndrome carrier and newborn screening. Genet. Med. 12, 162–173.CrossRefGoogle Scholar
  7. Hawkins M., Boyle J., Wright K. E., Elles R., Ramsden S. C., O’Grady A. et al. 2011 Preparation and validation of the first WHO international genetic reference panel for Fragile X syndrome. Eur. J. Hum. Genet. 19, 10–17.CrossRefGoogle Scholar
  8. Lyon E., Laver T., Yu P., Jama M., Young K., Zoccoli M. et al. 2010 A simple, high-throughput assay for Fragile X expanded alleles using triple repeat primed PCR and capillary electrophoresis. J. Mol. Diagn. 12, 505–511.CrossRefGoogle Scholar
  9. Monaghan K. G., Lyon E. and Spector E. B. 2013 ACMG Standards and Guidelines for fragile X testing: a revision to the disease-specific supplements to the standards and guidelines for clinical genetics laboratories of the American College of Medical Genetics and Genomics. Genet. Med. 15, 575–586.CrossRefGoogle Scholar
  10. Murray A., Webb J., Dennis N., Conway G. and Morton N. 1999 Microdeletions in FMR2 may be a significant cause of premature ovarian failure. J. Med. Genet. 36, 767–770.CrossRefGoogle Scholar
  11. Nolin S. L., Glicksman A., Ding X., Ersalesi N., Brown W. T., Sherman S. L. et al. 2011 Fragile X analysis of 1112 prenatal samples from 1991 to 2010. Prenat. Diagn. 31, 925–931.CrossRefGoogle Scholar
  12. Nygren A. O., Ameziane N., Duarte H. M., Vijzelaar R. N., Waisfisz Q., Hess C. J. et al. 2005 Methylation-specific MLPA (MS-MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences. Nucleic Acids Res. 33, e128.CrossRefGoogle Scholar
  13. Nygren A. O., Lens S. I. and Carvalho R. 2008 Methylation-specific multiplex ligation-dependent probe amplification enables a rapid and reliable distinction between male FMR1 premutation and full-mutation alleles. J. Mol. Diagn. 10, 496–501.CrossRefGoogle Scholar
  14. Peprah E. 2012 Fragile X syndrome: the FMR1 CGG repeat distribution among world populations. Ann. Hum. Genet. 76, 178–191.CrossRefGoogle Scholar
  15. Pouya A. R., Abedini S. S., Mansoorian N., Behjati F., Nikzat N., Mohseni M. et al. 2009 Fragile X syndrome screening of families with consanguineous and non-consanguineous parents in the Iranian population. Eur. J. Med. Genet. 52, 170–173.CrossRefGoogle Scholar
  16. Pretto D., Yrigollen C. M., Tang H. T., Williamson J., Espinal G., Iwahashi C. K. et al. 2014 Clinical and molecular implications of mosaicism in FMR1 full mutations. Front Genet. 5, 318.CrossRefGoogle Scholar
  17. Rajaratnam A., Shergill J., Salcedo-Arellano M., Saldarriaga W., Duan X. and Hagerman R. 2017 Fragile X syndrome and fragile X-associated disorders. F1000Res 6, 2112.CrossRefGoogle Scholar
  18. Rife M., Badenas C., Mallolas J., Jimenez L., Cervera R., Maya A. et al. 2003 Incidence of fragile X in 5,000 consecutive newborn males. Genet. Test 7, 339–343.CrossRefGoogle Scholar
  19. Stuppia L., Antonucci I., Palka G. and Gatta V. 2012 Use of the MLPA assay in the molecular diagnosis of gene copy number alterations in human genetic diseases. Int. J. Mol. Sci. 13, 3245–3276.CrossRefGoogle Scholar
  20. Suhl J. A. and Warren S. T. 2015 Single-nucleotide mutations in FMR1 reveal novel functions and regulatory mechanisms of the fragile X syndrome protein FMRP. J. Exp. Neurosci. 9, 35–41.PubMedPubMedCentralGoogle Scholar
  21. Todorov T., Todorova A., Kirov A., Dimitrov B., Carvalho R., Nygren A. O. et al. 2009 Fragile X mosaic male full mutation/normal allele detected by PCR/MS-MLPA. BMJ Case Rep. 2009.Google Scholar
  22. Tural S., Tekcan A., Kara N., Elbistan M., Guven D. and Ali Tasdemir H. 2015 FMR1 gene mutation screening by TP-PCR in patients with premature ovarian failure and fragile-X. Gynecol. Endocrinol. 31, 191–195.CrossRefGoogle Scholar
  23. Tzeng C. C., Tzeng P. Y., Sun H. S., Chen R. M. and Lin S. J. 2000 Implication of screening for FMR1 and FMR2 gene mutation in individuals with nonspecific mental retardation in Taiwan. Diagn. Mol. Pathol. 9, 75–80.CrossRefGoogle Scholar
  24. Wheeler A. C., Bailey D. B., Jr., Berry-Kravis E., Greenberg J., Losh M., Mailick M. et al. 2014 Associated features in females with an FMR1 premutation. J. Neurodev. Disord. 6, 30.CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2020

Authors and Affiliations

  • Zeinab Salimy
    • 1
  • Mohammad Taghi Akbari
    • 2
    Email author
  • Faravareh Khordadpoor Deilamani
    • 2
  1. 1.Department of Biology, Science and Research BranchIslamic Azad UniversityTehranIran
  2. 2.Tehran Medical Genetics LaboratoryTehranIran

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