Hum. Reprod. Advance Access originally published online on December 16, 2005
Human Reproduction 2006 21(4):952-957; doi:10.1093/humrep/dei432
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Influence of intermediate and uninterrupted FMR1 CGG expansions in premature ovarian failure manifestation
1 Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, 2 Institute of Molecular Genetics-CNR, Pavia, 3 Department of Experimental and Environmental Medicine and Medical Biotechnology, University of Milan-Bicocca, Monza, 4 Dibit-San Raffaele Scientific Institute, Milan and 5 Department of Obstetrics and Gynecology, University of Milan, Italy
6 To whom correspondence should be addressed at: Department of Biology and Genetics for Medical Sciences, University of Milan, Via Viotti 3/5, 20133 Milan, Italy. E-mail: anna.marozzi{at}unimi.it
BACKGROUND: Studies attempting to precisely define the range of fragile mental retardation 1 (FMR1) expansions and its inf luence in premature ovarian failure (POF) manifestation are partially lacking. To this aim, we evaluated a large cohort of POF patients for the size and, in selected cases, for the sequence of the CGG expansion. Furthermore, the correlation between POF and X-inactivation was investigated in FRAXA families. METHODS: By fluorescent PCR, 190 POF and 200 control women were sized for the CGG tract; some subjects were also characterized by sequencing and for the FMR1 activation ratio. RESULTS AND CONCLUSION: We found a significant association (19/190, 10%, P < 1 x 10–6) between POF and FMR1 premutation (range 63–163 repeats) and a significant enrichment (9/190, 4.7%, P = 0.021) of POF carriers of intermediate expansions (range 41–58 repeats). Interestingly, intermediate alleles were entirely composed of CGG repeats. Furthermore, the analysis of three pairs of siblings with similar FMR1 expansions and discordant for the POF phenotype showed a direct correlation between the expression of the intermediate/premutated allele and POF manifestation. The results obtained strengthen the correlation between FMR1 expansion and POF and suggest that the manifestation of the ovarian dysfunction could be influenced both by the pattern of interruption of the CGG repeat and by X-inactivation.
Key words: AGG interruption/CGG length/FMR1 expansion/POF/X-inactivation pattern
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Corre, J. Schuettler, S. Bione, A. Marozzi, L. Persani, R. Rossetti, F. Torricelli, I. Giotti, P. Vogt, D. Toniolo, et al. A large-scale association study to assess the impact of known variants of the human INHA gene on premature ovarian failure Hum. Reprod., August 1, 2009; 24(8): 2023 - 2028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. W. Hayes and R. Matalon Fragile X Syndrome Pediatrics, August 1, 2009; 124(2): 790 - 792. [Full Text] [PDF]
|
|
|
|
 |
|
 The ESHRE Capri Workshop Group Genetic aspects of female reproduction Hum. Reprod. Update, April 2, 2008; (2008) dmn009v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Z Loesch, Q. M Bui, R. M Huggins, R. J Mitchell, R. J Hagerman, and F. Tassone Transcript levels of the intermediate size or grey zone fragile X mental retardation 1 alleles are raised, and correlate with the number of CGG repeats J. Med. Genet., March 1, 2007; 44(3): 200 - 204. [Abstract] [Full Text] [PDF]
|
|