Improved Molecular Diagnostics of Idiopathic Short Stature and Allied Disorders: Quantitative Polymerase Chain Reaction-Based Copy Number Profiling of SHOX and Pseudoautosomal Region 1

被引:12
作者
D'haene, Barbara [1 ]
Hellemans, Jan [1 ]
Craen, Margarita [2 ]
De Schepper, Jean [2 ]
Devriendt, Koen [3 ]
Fryns, Jean-Pierre [3 ]
Keymolen, Kathelijn [4 ]
Debals, Eveline [1 ]
de Klein, Annelies [5 ]
de Jong, Elisabeth M. [5 ]
Segers, Karin [6 ]
De Paepe, Anne [1 ]
Mortier, Geert [1 ]
Vandesompele, Jo [1 ]
De Baere, Elfride [1 ]
机构
[1] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium
[2] Ghent Univ Hosp, Dept Paediat, B-9000 Ghent, Belgium
[3] Leuven Univ Hosp, Ctr Human Genet, B-3000 Louvain, Belgium
[4] Free Univ Brussels, Ctr Med Genet, B-1090 Brussels, Belgium
[5] Erasmus MC, NL-3075 EA Rotterdam, Netherlands
[6] Univ Liege, Ctr Human Genet, B-4000 Liege, Belgium
关键词
LERI-WEILL DYSCHONDROSTEOSIS; GROWTH-HORMONE TREATMENT; RAPID DETECTION; GENE; PCR; DELETIONS; DOWNSTREAM; HAPLOINSUFFICIENCY; DEFICIENCY; GUIDELINES;
D O I
10.1210/jc.2009-2218
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: Short stature has an incidence of three in 100 in children. Reliable molecular genetic testing may be crucial in the context of beneficial disease management. Deletions spanning or surrounding the SHOX gene account for a significant proportion of patients with idiopathic short stature (ISS) and allied disorders, such as Leri-Weill dyschondrosteosis. Objective: Several shortcomings of current strategies for copy number profiling of the SHOX region prompted us to develop an improved test for molecular diagnostics of the SHOX region. Design and Results: We introduced a quantitative PCR (qPCR)-based copy number profiling test, consisting of 11 amplicons targeting clinically relevant regions, i.e. the SHOX gene and regulatory regions. To ensure an optimal sensitivity and specificity, this test was validated in 32 controls and 18 probands with previously identified copy number changes. In addition, 152 probands with SHOX-associated phenotypes were screened, revealing 10 novel copy number changes. Conclusion: This highly validated qPCR test supersedes other approaches for copy number screening of the SHOX region in terms of reliability, accuracy, and cost efficiency. In addition, another strong point is the fact that it can be easily implemented in any standard equipped molecular laboratory. Our qPCR-based test is highly recommended for molecular diagnostics of idiopathic short stature and allied disorders. (J Clin Endocrinol Metab 95: 3010-3018, 2010)
引用
收藏
页码:3010 / 3018
页数:9
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