title: Ovarian dysfunction and FMR1 alleles in a large Italian family with POF and FRAXA disorders: case report.
abstract: BACKGROUND
  The association between premature ovarian failure (POF) and the FMR1 repeat number (41> CGGn< 200) has been widely investigated. Current findings suggest that the risk estimation for POF can be calculated in the offspring of women with pre-mutated FMR1 alleles.
  
  
  METHODS
  We describe the coexistence in a large Italian kindred of Fragile X syndrome and familial POF in females with ovarian dysfunctions who carried normal or expanded FMR1 alleles. Genetic analysis of the FMR1 gene in over three generations of females revealed that six carried pre-mutated alleles (61-200), of which two were also affected by POF. However a young woman, who presented a severe ovarian failure with early onset, carried normal FMR1 alleles (<40). The coexistence within the same family of two dysfunctional ovarian conditions, one FMR1-related and one not FMR1-related, suggests that the complexity of familial POF conditions is larger than expected.
  
  
  CONCLUSIONS
  Our case study represents a helpful observation and will provide familial cases with heterogeneous etiology that could be further studied when candidate genes in addition to the FMR1 premutation will be available.
authors.affiliation: Institute of Genetics and Biophysics, Adriano Buzzati Traverso, CNR, Naples, Italy. miano@igb.cnr.it
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Miano
authors.forename: Carmela
authors.initials: C
authors.lastname: Laperuta
authors.forename: Pietro
authors.initials: P
authors.lastname: Chiurazzi
authors.forename: Michele
authors.initials: M
authors.lastname: D'Urso
authors.forename: Matilde Valeria
authors.initials: MV
authors.lastname: Ursini
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000150:complications / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016649:Primary Ovarian Insufficiency / Q000150:complications / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion; D049951:X Chromosome Inactivation
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human