title: Fragile X syndrome in females - a familial case report and review of the literature.
abstract: BACKGROUND
  Fragile X syndrome (FXS), one of the manifestations of FMR1-related disorders, is one of the most frequent genetic causes of intellectual disability. In over 99% of all cases it results from the expansion of CGG repeats in the 5'-untranslated region of the FMR1 gene and presents in males and in about 50% of the females with an FMR1 full mutation, usually with a milder phenotype.
  
  
  OBJECTIVE
  Although the morphologic and behavioral phenotype in males is a well-recognized entity, the presentation in females is variable and not as specific. The objective of this paper is to present a family with quite a severe expression of the disorder in two sisters with a full mutation.
  
  
  METHODS
  We report on a two-generation family where both males and females were found to be affected by FXS. We also present the diagnostic pathway and methods that led to the diagnosis of fragile X syndrome in the two sisters, as well as the method that explained the normal phenotype in their mother.
  
  
  RESULTS
  The CGG repeats analysis in the FMR1 gene showed one normal allele and one allele with a full mutation in both sisters (probands) and their mother. A full mutation was also found in three male cousins of the probands. The analysis of the X-chromosome methylation status has shown a random X inactivation in proband 1 and 2 and a non-random one in the proband's mother, with the normal allele predominantly active.
  
  
  CONCLUSIONS
  The reasons for different clinical presentations are discussed; moreover a review of the literature on females with FXS is presented. We hope that this paper will facilitate the future diagnosis of fragile X syndromes in females.
authors.affiliation: Department of Genetics, Wroclaw Medical University, Marcinkowskiego Street 1, 50-368 Wroclaw, Poland tel. (+48 71) 784-12-61 fax (+48 71) 784-00-63 e-mail: agnieszka.stembalska@umed.wroc.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Stembalska
authors.affiliation: Department of Genetics, Wroclaw Medical University, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Łaczmańska
authors.affiliation: Department of Genetics, Wroclaw Medical University, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Gil
authors.affiliation: Department of Genetics, Wroclaw Medical University, Poland.
authors.forename: Karolina A
authors.initials: KA
authors.lastname: Pesz
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: FMR1 gene; X-inactivation; female; fragile X syndrome; intellectual disability