Influence of intermediate and uninterrupted FMR1 CGG expansions in premature ovarian failure manifestation
Articolo
Data di Pubblicazione:
2006
Citazione:
Influence of intermediate and uninterrupted FMR1 CGG expansions in premature ovarian failure manifestation / B. Bodega, S. Bione, L. Dalpra, D. Toniolo, F. Ornaghi, W. Vegetti, E. Ginelli, A. Marozzi. - In: HUMAN REPRODUCTION. - ISSN 0268-1161. - 21:4(2006), pp. 952-957. [10.1093/humrep/dei432]
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
AGG interruption; CGG length; FMR1 expansion; POF; X-inactivation pattern
Elenco autori:
B. Bodega, S. Bione, L. Dalpra, D. Toniolo, F. Ornaghi, W. Vegetti, E. Ginelli, A. Marozzi
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