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


METHODS
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.
Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
Carolina J
CJ
Jorgez
John W
JW
Weedin
Aysegul
A
Sahin
Mounia
M
Tannour-Louet
Shuo
S
Han
Juan C
JC
Bournat
Anna
A
Mielnik
Sau Wai
SW
Cheung
Ajay K
AK
Nangia
Peter N
PN
Schlegel
Larry I
LI
Lipshultz
Dolores J
DJ
Lamb
D000328:Adult; D001827:Body Height / Q000235:genetics; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011544:Pseudogenes / Q000235:genetics*; D012729:Sex Chromosome Aberrations; D058533:Sex Chromosome Disorders of Sex Development / Q000235:genetics; D000074122:Short Stature Homeobox Protein
D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein
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