title: Recurrent X chromosome-linked deletions: discovery of new genetic factors in male infertility.
abstract: BACKGROUND
  The role of X-linked genes and copy-number variations (CNVs) in male infertility remains poorly explored. Our previous array-CGH analyses showed three recurrent deletions in Xq exclusively (CNV67) and prevalently (CNV64, CNV69) found in patients. Molecular and clinical characterisation of these CNVs was performed in this study.
  
  
  METHODS
  627 idiopathic infertile patients and 628 controls were tested for each deletion with PCR+/-. We used PCR+/- to map deletion junctions and long-range PCR and direct sequencing to define breakpoints.
  
  
  RESULTS
  CNV64 was found in 5.7% of patients and in 3.1% of controls (p=0.013; OR=1.89; 95% CI 1.1 to 3.3) and CNV69 was found in 3.5% of patients and 1.6% of controls (p=0.023; OR=2.204; 95% CI 1.05 to 4.62). For CNV69 we identified two breakpoints, types A and B, with the latter being significantly more frequent in patients than controls (p=0.011; OR=9.19; 95% CI 1.16 to 72.8). CNV67 was detected exclusively in patients (1.1%) and was maternally transmitted. The semen phenotype of one carrier (11-041) versus his normozoospermic non-carrier brother strongly indicates a pathogenic effect of the deletion on spermatogenesis. MAGEA9, an ampliconic gene reported as independently acquired on the human X chromosome with exclusive physiological expression in the testis, is likely to be involved in CNV67.
  
  
  CONCLUSIONS
  We provide the first evidence for X chromosome-linked recurrent deletions associated with spermatogenic impairment. CNV67, specific to spermatogenic anomaly and with a frequency of 1.1% in oligo/azoospermic men, resembles the AZF regions on the Y chromosome with potential clinical implications.
authors.affiliation: Molecular Biology Laboratory, Fundació Puigvert Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Lo Giacco
authors.forename: C
authors.initials: C
authors.lastname: Chianese
authors.forename: E
authors.initials: E
authors.lastname: Ars
authors.forename: E
authors.initials: E
authors.lastname: Ruiz-Castañé
authors.forename: G
authors.initials: G
authors.lastname: Forti
authors.forename: C
authors.initials: C
authors.lastname: Krausz
mesh_terms: D053713:Azoospermia / Q000235:genetics; D016022:Case-Control Studies; D041321:Chromosomes, Human, X; D018628:Gene Dosage; D050172:Genes, X-Linked; D056726:Genetic Association Studies; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017384:Sequence Deletion; D013091:Spermatogenesis / Q000235:genetics