title: Allelic variants in HOX genes in cryptorchidism.
abstract: BACKGROUND
  Cryptorchidism is one of the most common congenital anomalies and is associated with increased risk for infertility and testicular cancer later in life. Findings from animal models and small clinical studies suggest that the posterior HOX genes (paralogs 9-13) could be potential candidate genes for cryptorchidism and that the HOX genes are functionally redundant within paralogous groups.
  
  
  METHODS
  The coding regions and exon-intron boundaries of the 16 posterior HOX genes were sequenced and analyzed in group 1 (44 nonsyndromic cryptorchidism cases and 46 healthy controls). Those specific variants found to be significantly different between cases and controls in group 1 were examined in DNA from group 2 (108 cases and 114 controls).
  
  
  RESULTS
  A total of 57 variants was found in group 1, among which the allele frequency of 180A>G (A60A) in HOXD13 alone was significantly elevated in cases versus controls (P = 0.02). In the combined 1 + 2 group, cases were also more likely than controls to have the G allele (P = 0.002). As predicted by an exonic splicing enhancer finder program, the 180A>G (A60A) variant is expected to have an influence on the splicing of transcripts from HOXD13. In group 1, case subjects were more likely to carry multiple variants in HOXA13 and HOXD13 (P = 0.02) than controls.
  
  
  CONCLUSIONS
  The variant 180A>G (A60A) in HOXD13 is a risk factor for cryptorchidism, and a dynamic equilibrium of genes in HOX paralog 13 is involved in the pathogenesis of cryptorchidism.
authors.affiliation: Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. wangy@email.chop.edu
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Julia
authors.initials: J
authors.lastname: Barthold
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.forename: Tracy
authors.initials: T
authors.lastname: Casalunovo
authors.forename: Erin
authors.initials: E
authors.lastname: Pearson
authors.forename: Jeanne
authors.initials: J
authors.lastname: Manson
mesh_terms: D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics; D016022:Case-Control Studies; D003456:Cryptorchidism / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D050436:Regulatory Elements, Transcriptional
chemical_list: D018398:Homeodomain Proteins