title: Improved molecular diagnostics of idiopathic short stature and allied disorders: quantitative polymerase chain reaction-based copy number profiling of SHOX and pseudoautosomal region 1.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: D'haene
authors.forename: Jan
authors.initials: J
authors.lastname: Hellemans
authors.forename: Margarita
authors.initials: M
authors.lastname: Craen
authors.forename: Jean
authors.initials: J
authors.lastname: De Schepper
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Kathelijn
authors.initials: K
authors.lastname: Keymolen
authors.forename: Eveline
authors.initials: E
authors.lastname: Debals
authors.forename: Annelies
authors.initials: A
authors.lastname: de Klein
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: de Jong
authors.forename: Karin
authors.initials: K
authors.lastname: Segers
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Geert
authors.initials: G
authors.lastname: Mortier
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.forename: Elfride
authors.initials: E
authors.lastname: De Baere
mesh_terms: D001827:Body Height / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics; D015331:Cohort Studies; D003198:Computer Simulation; D004247:DNA / Q000235:genetics; D056915:DNA Copy Number Variations; D017931:DNA Primers; D005784:Gene Amplification; D006130:Growth Disorders / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000502:physiology; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074122:Short Stature Homeobox Protein
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein; D004247:DNA