Aberrations in Pseudoautosomal Regions (PARs) Found in Infertile Men with Y-Chromosome Microdeletions

• Published in: The journal of clinical endocrinology and metabolism Vol. 96; no. 4; pp. E674 - E679
• Main Authors: Jorgez, Carolina J., Weedin, John W., Sahin, Aysegul, Tannour-Louet, Mounia, Han, Shuo, Bournat, Juan C., Mielnik, Anna, Cheung, Sau Wai, Nangia, Ajay K., Schlegel, Peter N., Lipshultz, Larry I., Lamb, Dolores J.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.04.2011; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adult; Body Height - genetics; Case-Control Studies; Chromosome Aberrations; Chromosome Deletion; Chromosome rearrangements; Chromosomes, Human, Y - genetics; Comparative Genomic Hybridization; DNA Copy Number Variations; Genomics; Homeodomain Proteins - genetics; Humans; Hybridization; In Situ Hybridization, Fluorescence; Infertility; Infertility, Male - genetics; JCEM Online: Brief Reports; Karyotypes; Male; Meiosis; Middle Aged; Pseudogenes - genetics; Sex Chromosome Aberrations; Sex Chromosome Disorders of Sex Development - genetics; Short Stature Homeobox Protein; Y chromosomes
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2010-2018

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.