title: Double trisomy in spontaneous miscarriages: cytogenetic and molecular approach.
abstract: BACKGROUND
  Although single trisomy is the most common chromosomal abnormality observed within first trimester spontaneous abortions (SA) (>50%), double trisomy (DT) ranges from 0.21 to 2.8% in the literature. Since little is known about mechanisms underlying DT, we report the results of our experience with 517 SA, establishing parental origin and cell stage of non-disjunction when possible in DT cases, and making a revision of those previously reported.
  
  
  METHODS
  Cytogenetic analysis was performed in all aborted specimens. Quantitative fluorescent PCR (QF-PCR) and multiplex ligation-dependent probe amplification (MLPA) were performed in DT cases in order to assess parental origin and stage of error of aneuploidy in addition to its reliability in detecting aneuploidies.
  
  
  RESULTS
  Karyotyping was successful in 321 miscarriages; the rate of DT was 2.18%. Among the seven DT cases reported, three new combinations were found. Maternal origin was established for all DT SA analysed. Meiotic stage of error was presumed meiosis I (MI) for 48,XX+15+22 and 48,XX+8+21, meiosis II (MII) for 48,XXX+18, and MII and MI respectively for 48,XY+18+22. Molecular results agreed with cytogenetic results.
  
  
  CONCLUSIONS
  Similar maternal age-related mechanisms could be implicated in both single and double trisomy. Molecular techniques could be useful in diagnosing not only single but multiple aneuploidy and determining its origin. This will improve our knowledge about mechanisms underlying human aneuploidy, and enable appropriate genetic counselling.
authors.affiliation: Human Genetics, Fundacion Jimenez Diaz, Avda Reyes Católicos 2, 28040, Madrid, Spain. ddiego@fjd.es
authors.forename: Dan
authors.initials: D
authors.lastname: Diego-Alvarez
authors.forename: Carmen
authors.initials: C
authors.lastname: Ramos-Corrales
authors.forename: Maria
authors.initials: M
authors.lastname: Garcia-Hoyos
authors.forename: Ana
authors.initials: A
authors.lastname: Bustamante-Aragones
authors.forename: Diego
authors.initials: D
authors.lastname: Cantalapiedra
authors.forename: Joaquin
authors.initials: J
authors.lastname: Diaz-Recasens
authors.forename: Elena
authors.initials: E
authors.lastname: Vallespin-Garcia
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: Isabel
authors.initials: I
authors.lastname: Lorda-Sanchez
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D005260:Female; D006801:Humans; D007621:Karyotyping; D008423:Maternal Age; D008540:Meiosis / Q000502:physiology; D009630:Nondisjunction, Genetic; D016133:Polymerase Chain Reaction; D014314:Trisomy