Aberrations in pseudoautosomal regions (PARs) found in infertile men with Y-chromosome microdeletions

J Clin Endocrinol Metab. 2011 Apr;96(4):E674-9. doi: 10.1210/jc.2010-2018. Epub 2011 Jan 20.

Abstract

Context: The pseudoautosomal regions (PARs) of the Y-chromosome undergo meiotic recombination with the X-chromosome. PAR mutations are associated with infertility and mental and stature disorders.

Objective: The aim of the study was to determine whether men with Y-chromosome microdeletions have structural defects in PARs.

Design and participants: Eighty-seven infertile men with Y-chromosome microdeletions and 35 controls were evaluated for chromosomal rearrangements using commercial or custom (X- and Y-chromosome) array comparative genomic hybridization or by quantitative PCR of selected PAR genes. Multisoftware-defined chromosomal gains or losses were validated by quantitative PCR and FISH.

Results: Array comparative genomic hybridization confirmed the AZF deletions identified by multiplex PCR. All men with Y-chromosome microdeletions and an abnormal karyotype displayed PAR abnormalities, as did 10% of men with Y-chromosome microdeletions and a normal karyotype. None of the control subjects or infertile men without Y-chromosome microdeletions had PAR duplications or deletions. SHOX aberrations occurred in 14 men (nine gains and five losses); four were short in stature (<10th percentile), and one was tall (>95th percentile). In contrast, the height of 23 men with Y-chromosome microdeletions and normal PARs was average at 176.8 cm (50th percentile).

Conclusions: Y-chromosome microdeletions can include PAR defects causing genomic disorders such as SHOX, which may be transmitted to offspring. Previously unrecognized PAR gains and losses in men with Y-chromosome microdeletions may have consequences for offspring.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Adult
  • Body Height / genetics
  • Case-Control Studies
  • Chromosome Aberrations*
  • Chromosome Deletion
  • Chromosomes, Human, Y / genetics
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations
  • Homeodomain Proteins / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infertility, Male / genetics*
  • Male
  • Middle Aged
  • Pseudogenes / genetics*
  • Sex Chromosome Aberrations
  • Sex Chromosome Disorders of Sex Development / genetics
  • Short Stature Homeobox Protein

Substances

  • Homeodomain Proteins
  • SHOX protein, human
  • Short Stature Homeobox Protein

Supplementary concepts

  • Male sterility due to Y-chromosome deletions