title: Analysis of the molecular parameters that could predict the risk of manifesting premature ovarian failure in female premutation carriers of fragile X syndrome.
abstract: 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.
authors.affiliation: Molecular Genetics Laboratory, Cruces Hospital, Barakaldo, Bizkaia. mariaisabel.tejadaminguez@sakidetza.net
authors.forename: Maria-Isabel
authors.initials: MI
authors.lastname: Tejada
authors.forename: Eva
authors.initials: E
authors.lastname: García-Alegría
authors.forename: Amaia
authors.initials: A
authors.lastname: Bilbao
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez-Bouzas
authors.forename: Elena
authors.initials: E
authors.lastname: Beristain
authors.forename: Marisa
authors.initials: M
authors.lastname: Poch
authors.forename: Maria A
authors.initials: MA
authors.lastname: Ramos-Arroyo
authors.forename: Blanca
authors.initials: B
authors.lastname: López
authors.forename: Isabel
authors.initials: I
authors.lastname: Fernandez Carvajal
authors.forename: Maria-Pilar
authors.initials: MP
authors.lastname: Ribate
authors.forename: Feliciano
authors.initials: F
authors.lastname: Ramos
mesh_terms: 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
chemical_list: D004268:DNA-Binding Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; C106905:CGGBP1 protein, human