Mol. Hum. Reprod. Advance Access originally published online on August 24, 2007
Molecular Human Reproduction 2007 13(10):745-750; doi:10.1093/molehr/gam053
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A simple screening method for detection of Klinefelter syndrome and other X-chromosome aneuploidies based on copy number of the androgen receptor gene
Department of Growth and Reproduction, Juliane Marie Centre, Section GR-5064, The National University Hospital of Copenhagen, DK-2100 Copenhagen, Denmark
1 Correspondence address. Tel: +45-35-45-43-30; Fax: +45-35-45-60-54; E-mail: anne.marie.ottesen{at}rh.regionh.dk
Due to the high prevalence and variable phenotype of patients with Klinefelter syndrome, there is a need for a robust and rapid screening method allowing early diagnosis. Here, we report on the development and detailed clinical validation of a quantitative real-time PCR (qPCR)-based method of the copy number assessment of the androgen receptor (AR) gene, located to Xq11.2–q12. We analysed samples from 50 individuals, including a healthy male and female controls and patients with Klinefelter syndrome (47,XXY; 48,XXXY) (n = 28), mosaicisms (46,XX/47,XXY/48XXYY; 45,X/46,XY) (n = 3), other sex chromosome abnormalities (46,XX males; 47,XYY)(n = 4) and normal karyotypes (46,XY) (n = 13). The reference range for the AR-copy number was established as 0.8–1.2 for one copy and 1.7–2.3 for two copies. The qPCR results were within the reference range in 17/18 samples (94%) or 30/31 (97%) samples with one or two copies of the AR gene, respectively. None of the Klinefelter patients were misdiagnosed as having a karyotype with only one X-chromosome, and in none of the 46,XY males were two copies demonstrated. We systematically compared qPCR results with those obtained with another PCR-based method, the XIST-gene expression. The XIST-expression based assay was correct in only 29/36 samples (81%). Our findings demonstrated that the AR-qPCR technique is a simple and reliable screening method for diagnosis of patients with Klinefelter syndrome or other chromosomal disorders involving an aberrant number of X-chromosomes.
Key words: Klinefelter syndrome/qPCR technique/screening/X-chromosome
Submitted on July 6, 2007; accepted on July 17, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Mau Kai, A. Juul, K. McElreavey, A.M. Ottesen, I.D. Garn, K.M. Main, A. Loft, N. Jorgensen, N.E. Skakkebaek, A. Nyboe Andersen, et al. Sons conceived by assisted reproduction techniques inherit deletions in the azoospermia factor (AZF) region of the Y chromosome and the DAZ gene copy number Hum. Reprod., April 25, 2008; (2008) den124v1. [Abstract] [Full Text] [PDF]
|
|