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.
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.
Authors: Sara Benito-Sanz; Alberta Belinchon-Martínez; Miriam Aza-Carmona; Carolina de la Torre; Celine Huber; Isabel González-Casado; Judith L Ross; N Simon Thomas; Andrew R Zinn; Valerie Cormier-Daire; Karen E Heath Journal: J Hum Genet Date: 2016-09-08 Impact factor: 3.172
Authors: Erwin Brosens; Elisabeth M de Jong; Tahsin Stefan Barakat; Bert H Eussen; Barbara D'haene; Elfride De Baere; Hannah Verdin; Pino J Poddighe; Robert-Jan Galjaard; Joost Gribnau; Alice S Brooks; Dick Tibboel; Annelies de Klein Journal: Eur J Hum Genet Date: 2014-01-08 Impact factor: 4.246
Authors: Charlotte D'Hulst; Irena Parvanova; Delia Tomoiaga; Maria L Sapar; Paul Feinstein Journal: Stem Cell Reports Date: 2013-09-26 Impact factor: 7.765
Authors: Hannah Verdin; Ana Fernández-Miñán; Sara Benito-Sanz; Sandra Janssens; Bert Callewaert; Kathleen De Waele; Jean De Schepper; Inge François; Björn Menten; Karen E Heath; José Luis Gómez-Skarmeta; Elfride De Baere Journal: Sci Rep Date: 2015-12-03 Impact factor: 4.379