title: X-chromosome terminal deletion in a female with premature ovarian failure: Haploinsufficiency of X-linked genes as a possible explanation.
abstract: BACKGROUND
  Premature ovarian failure (POF) has repeatedly been associated to X-chromosome deletions. FMR1 gene premutation allele's carrier women have an increased risk for POF. We intent to determine the cause of POF in a 29 year old female, evaluating both of these situations.
  
  
  METHODS
  Concomitant analysis of FMR1 gene CGG repeat number and karyotype revealed an X-chromosome terminal deletion. Fluorescence in situ further characterized the breakpoint. A methylation assay for FMR1 gene allowed to determine its methylation status, and hence, the methylation status of the normal X-chromosome.
  
  
  RESULTS
  We report a POF patient with a 46,X,del(X)(q26) karyotype and with skewed X-chromosome inactivation of the structural abnormal X-chromosome.
  
  
  CONCLUSIONS
  Despite the hemizygosity of FMR1 gene, the patient does not present Fragile X syndrome features, since the normal X-chromosome is not subject to methylation. The described deletion supports the hypothesis that haploinsufficiency of X-linked genes can be on the basis of POF, and special attention should be paid to X-linked genes in region Xq28 since they escape inactivation and might have a role in this disorder. A full clinical and cytogenetic characterization of all POF cases is important to highlight a pattern and help to understand which genes are crucial for normal ovarian development.
authors.affiliation: Laboratório de Citogenética, Instituto de Biologia Médica, Faculdade de Medicina, Universidade de Coimbra, 3000-354 Coimbra, Portugal. i_marques@hotmail.com.
authors.forename: Susana I
authors.initials: SI
authors.lastname: Ferreira
authors.forename: Eunice
authors.initials: E
authors.lastname: Matoso
authors.forename: Marta
authors.initials: M
authors.lastname: Pinto
authors.forename: Joana
authors.initials: J
authors.lastname: Almeida
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.forename: Joana B
authors.initials: JB
authors.lastname: Melo
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Carreira