Improved molecular diagnostics of idiopathic short stature and allied disorders: quantitative polymerase chain reaction-based copy number profiling of SHOX and pseudoautosomal region 1

Barbara D'haene, Jan Hellemans, Margarita Craen, Jean De Schepper, Koen Devriendt, Jean-Pierre Fryns, Kathelijn Keymolen, Eveline Debals, Annelies de Klein, Elisabeth M de Jong, Karin Segers, Anne De Paepe, Geert Mortier, Jo Vandesompele, Elfride De Baere

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3010-8
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume95
Issue number6
DOIs
Publication statusPublished - Jun 2010

Keywords

  • Body Height
  • Chromosomes, Human, X
  • Cohort Studies
  • Computer Simulation
  • DNA
  • DNA Copy Number Variations
  • DNA Primers
  • Gene Amplification
  • Growth Disorders
  • Homeodomain Proteins
  • Humans
  • Mutation
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Research Support, Non-U.S. Gov't

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