Analysis of the molecular parameters that could predict the risk of manifesting premature ovarian failure in female premutation carriers of fragile X syndrome.
OBJECTIVE
To study three molecular parameters (number of CGG repeats, X-inactivation ratio, and expression of FMR1 mRNA) in premutation carriers of fragile X syndrome with and without premature ovarian failure (POF) to find differences between these two groups that could be useful in reproductive counseling.


METHODS
A retrospective clinical and molecular genetic study of 42 known premutation carriers of fragile X syndrome aged 40 years or older, 25 with POF and 17 without. A blood sample to obtain mRNA was taken from all of them. They all lived in five autonomous communities in northern Spain.


RESULTS
Although the relationship among mRNA levels, X-inactivation ratio, and CGG repeats seems to be similar both in women with POF and in those without: in women with POF, the effect of the CGG repeats on the mRNA levels was statistically significant (P = 0.0437), but in women without POF, it was not (P = 0.0724). Moreover, we confirmed previous results on the nonlinear association between CGG repeat number and the manifestation of POF, showing that the likelihood of having POF was significantly higher with fewer than 100 CGG repeats compared with 100 or more CGG repeats (odds ratio = 13.09, P = 0.0240).


CONCLUSIONS
Our present work suggests that mRNA and X-inactivation studies in blood are not relevant in predicting POF in female premutation carriers of fragile X syndrome. However, having a permutation of fewer than 100 repeats could represent a significant risk of POF.
Tejada
Maria-Isabel
MI
Molecular Genetics Laboratory, Cruces Hospital, Barakaldo, Bizkaia. mariaisabel.tejadaminguez@sakidetza.net
García-Alegría
Eva
E
Bilbao
Amaia
A
Martínez-Bouzas
Cristina
C
Beristain
Elena
E
Poch
Marisa
M
Ramos-Arroyo
Maria A
MA
López
Blanca
B
Fernandez Carvajal
Isabel
I
Ribate
Maria-Pilar
MP
Ramos
Feliciano
F
D000328:Adult; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics
D004268:DNA-Binding Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; C106905:CGGBP1 protein, human