Identification of 15 novel partial SHOX deletions and 13 partial duplications, and a review of the literature reveals intron 3 to be a hotspot region

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

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Short stature homeobox gene (SHOX) is located in the pseudoautosomal region 1 of the sex chromosomes. It encodes a transcription factor implicated in the skeletal growth. Point mutations, deletions or duplications of SHOX or its transcriptional regulatory elements are associated with two skeletal dysplasias, Léri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia (LMD), as well as in a small proportion of idiopathic short stature (ISS) individuals. We have identified a total of 15 partial SHOX deletions and 13 partial SHOX duplications in LWD, LMD and ISS patients referred for routine SHOX diagnostics during a 10 year period (2004-2014). Subsequently, we characterized these alterations using MLPA (multiplex ligation-dependent probe amplification assay), fine-tiling array CGH (comparative genomic hybridation) and breakpoint PCR. Nearly half of the alterations have a distal or proximal breakpoint in intron 3. Evaluation of our data and that in the literature reveals that although partial deletions and duplications only account for a small fraction of SHOX alterations, intron 3 appears to be a breakpoint hotspot, with alterations arising by non-allelic homologous recombination, non-homologous end joining or other complex mechanisms.

Original languageEnglish (US)
Pages (from-to)229-234
Number of pages6
JournalJournal of Human Genetics
Volume62
Issue number2
DOIs
StatePublished - Feb 1 2017

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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