title: Deletions and duplications of the 22q11.2 region in spermatozoa from DiGeorge/velocardiofacial fathers.
abstract: BACKGROUND
  DiGeorge/velocardiofacial syndrome (DGS/VCFS) is the most common deletion syndrome in humans. Low copy repeats flanking the 22q11.2 region confer a substrate for non-allelic homologous recombination (NAHR) events leading to rearrangements. This study sought to identify DGS/VCFS fathers with increased susceptibility to deletions and duplications at the 22q11.2 region in spermatozoa and to assess the particular contribution of intra-chromatid and/or inter-chromatid NAHR. Semen samples from nine DGS/VCFS fathers were analyzed by triple-color FISH using a probe combination that discriminated between normal, deleted and duplicated genotypes. Microsatellite analysis were performed in the parents and the affected children to determine the parental origin of the deleted chromosome 22.
  
  
  RESULTS
  A significant increase in 22q11.2 deletions was observed in the sperm of two out of nine DGS/VCFS fathers (odds ratio 2.03-fold, P < 0.01), and in both cases the deletion in the offspring was transmitted by the father. Patients with significant increases in sperm anomalies presented a disturbed deletion:duplication 1:1 ratio (P < 0.01).
  
  
  CONCLUSIONS
  Altogether, results support that intra-chromatid NAHR is the mechanism responsible for the higher rate of sperm deletions, which is directly related to the transmission of the deleted chromosome 22 to offspring. Accordingly, the screening of sperm anomalies in the 22q11.2 region should be taken into account in the genetic counseling of DGS/VCFS families.
authors.affiliation: Unitat de Biologia Cellular (Facultat de Biociències). Universitat Autònoma de Barcelona, 08193-Bellaterra, Cerdanyola del Vallès, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Vergés
authors.affiliation: Unitat de Biologia Cellular (Facultat de Biociències). Universitat Autònoma de Barcelona, 08193-Bellaterra, Cerdanyola del Vallès, Spain ; Current address: Wellcome Trust Center for Cell Biology, University of Edinburgh, Edinburgh, Scotland United Kingdom.
authors.forename: Oscar
authors.initials: O
authors.lastname: Molina
authors.affiliation: Secció de Genètica Clínica. Hospital Universitari Sant Joan de Déu, 08950-Esplugues de Llobregat, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Geán
authors.affiliation: Unitat de Biologia Cellular (Facultat de Biociències). Universitat Autònoma de Barcelona, 08193-Bellaterra, Cerdanyola del Vallès, Spain.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vidal
authors.affiliation: Unitat de Biologia Cellular (Facultat de Biociències). Universitat Autònoma de Barcelona, 08193-Bellaterra, Cerdanyola del Vallès, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Blanco
keywords: Deletions and duplications; DiGeorge/velocardiofacial syndrome; Non-allelic homologous recombination; Spermatozoa