Tags

Type your tag names separated by a space and hit enter

A simple screening method for detection of Klinefelter syndrome and other X-chromosome aneuploidies based on copy number of the androgen receptor gene.
Mol Hum Reprod. 2007 Oct; 13(10):745-50.MH

Abstract

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.

Links

Publisher Full Text
Aggregator Full Text

Authors+Show Affiliations

Ottesen AM
Department of Growth and Reproduction, Juliane Marie Centre, Section GR-5064, The National University Hospital of Copenhagen, DK-2100, Copenhagen, Denmark. anne.marie.ottesen@rh.regionh.dk
Garn ID
No affiliation info available
Aksglaede L
No affiliation info available
Juul A
No affiliation info available
Rajpert-De Meyts E
No affiliation info available

MeSH

AneuploidyChromosomes, Human, XFemaleGene DosageHumansIn Situ Hybridization, FluorescenceKaryotypingKlinefelter SyndromeMalePolymerase Chain ReactionRNA, Long NoncodingRNA, UntranslatedReceptors, Androgen

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17720778

Citation

Ottesen, A M., et al. "A Simple Screening Method for Detection of Klinefelter Syndrome and Other X-chromosome Aneuploidies Based On Copy Number of the Androgen Receptor Gene." Molecular Human Reproduction, vol. 13, no. 10, 2007, pp. 745-50.
Ottesen AM, Garn ID, Aksglaede L, et al. A simple screening method for detection of Klinefelter syndrome and other X-chromosome aneuploidies based on copy number of the androgen receptor gene. Mol Hum Reprod. 2007;13(10):745-50.
Ottesen, A. M., Garn, I. D., Aksglaede, L., Juul, A., & Rajpert-De Meyts, E. (2007). A simple screening method for detection of Klinefelter syndrome and other X-chromosome aneuploidies based on copy number of the androgen receptor gene. Molecular Human Reproduction, 13(10), 745-50.
Ottesen AM, et al. A Simple Screening Method for Detection of Klinefelter Syndrome and Other X-chromosome Aneuploidies Based On Copy Number of the Androgen Receptor Gene. Mol Hum Reprod. 2007;13(10):745-50. PubMed PMID: 17720778.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A simple screening method for detection of Klinefelter syndrome and other X-chromosome aneuploidies based on copy number of the androgen receptor gene. AU - Ottesen,A M, AU - Garn,I D, AU - Aksglaede,L, AU - Juul,A, AU - Rajpert-De Meyts,E, Y1 - 2007/08/24/ PY - 2007/8/28/pubmed PY - 2008/6/24/medline PY - 2007/8/28/entrez SP - 745 EP - 50 JF - Molecular human reproduction JO - Mol Hum Reprod VL - 13 IS - 10 N2 - 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. SN - 1360-9947 UR - https://www.unboundmedicine.com/medline/citation/17720778/A_simple_screening_method_for_detection_of_Klinefelter_syndrome_and_other_X_chromosome_aneuploidies_based_on_copy_number_of_the_androgen_receptor_gene_ L2 - https://academic.oup.com/molehr/article-lookup/doi/10.1093/molehr/gam053 DB - PRIME DP - Unbound Medicine ER -