title: Molecular genetic and cytogenetic characterization of a partial Xp duplication and Xq deletion in a patient with premature ovarian failure.
abstract: BACKGROUND
  The etiology of premature ovarian failure (POF) still remains undefined. Although the majority of clinical cases are idiopathic, there are possibilities of the underestimation of the most common etiologies, probably genetic causes. By reporting a case of POF with a partial Xp duplication and Xq deletion in spite of a cytogenetically 46,XX normal karyotype, we look forward that the genetic cause of POF will be investigated more methodically.
  
  
  METHODS
  We performed a basic and clinical study at a university hospital-affiliated fertility center. The study population was a POF patient and her family. Cytogenetic analysis, FMR1 gene analysis, multiplex ligation-dependent probe amplification (MLPA), fluorescent in situ hybridization (FISH), and oligonucleotide-array based comparative genomic hybridization (array CGH) were performed.
  
  
  RESULTS
  In spite of normal cytogenetic analysis in the proband and her mother and younger sister, FMR1 gene was not detected in the proband and her younger sister. In Southern blot analysis, the mother showed a normal female band pattern, but the proband and her younger sister showed no 5.2kb methylated band. The abnormal X chromosome of the proband and her sister was generated from the recombination of an inverted X chromosome of the mother during maternal meiosis, and the karyotype of the proband was 46,XX,rec(X)dup(Xp)inv(X)(p22.1q27.3).
  
  
  CONCLUSIONS
  Array CGH followed by FISH allowed precise characterization of the der(X) chromosome and the initial karyotype of the proband had been changed to 46,XX,rec(X)dup(Xp)inv(X)(p22.3q27.3)mat.arr Xp22.33p22.31(216519-8923527)x3,Xq27.3q28(144986425-154881514)x1. This study suggests that further genetic investigation may be needed in the cases of POF with a cytogenetically 46,XX normal karyotype to find out the cause and solution for these disease entities.
authors.affiliation: Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, College of Medicine, CHA University, Seoul 135-081, Republic of Korea.
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Hyun Ha
authors.initials: HH
authors.lastname: Seok
authors.forename: You Shin
authors.initials: YS
authors.lastname: Kim
authors.forename: Mi Uk
authors.initials: MU
authors.lastname: Chin
authors.forename: Se Ra
authors.initials: SR
authors.lastname: Sung
authors.forename: Woo Sik
authors.initials: WS
authors.lastname: Lee
authors.forename: Sung Han
authors.initials: SH
authors.lastname: Shim
authors.forename: Tae Ki
authors.initials: TK
authors.lastname: Yoon
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D058674:Chromosome Duplication / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D016649:Primary Ovarian Insufficiency / Q000235:genetics*
keywords: Amenorrhea; Array CGH; FISH; FSH; LH; MLPA; Mb; POF; Premature ovarian failure; Primary ovarian insufficiency; X chromosome aberration; array based comparative genomic hybridization; fluorescent in situ hybridization; follicle stimulating hormone; luteinizing hormone; megabase; multiplex ligation-dependent probe amplification; premature ovarian failure