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

4 Citations (Scopus)

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

Fingerprint

Homeobox Genes
Gene Deletion
Introns
Transcriptional Regulatory Elements
Sex Chromosomes
Gene Duplication
Homologous Recombination
Multiplex Polymerase Chain Reaction
Point Mutation
Transcription Factors
Polymerase Chain Reaction
Growth

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Benito-Sanz, S., Belinchon-Martínez, A., Aza-Carmona, M., De La Torre, C., Huber, C., González-Casado, I., ... Heath, K. E. (2017). 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. Journal of Human Genetics, 62(2), 229-234. https://doi.org/10.1038/jhg.2016.113

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. / Benito-Sanz, Sara; Belinchon-Martínez, Alberta; Aza-Carmona, Miriam; De La Torre, Carolina; Huber, Celine; González-Casado, Isabel; Ross, Judith L.; Thomas, N. Simon; Zinn, Andrew R.; Cormier-Daire, Valerie; Heath, Karen E.

In: Journal of Human Genetics, Vol. 62, No. 2, 01.02.2017, p. 229-234.

Research output: Contribution to journalArticle

Benito-Sanz, S, Belinchon-Martínez, A, Aza-Carmona, M, De La Torre, C, Huber, C, González-Casado, I, Ross, JL, Thomas, NS, Zinn, AR, Cormier-Daire, V & Heath, KE 2017, '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', Journal of Human Genetics, vol. 62, no. 2, pp. 229-234. https://doi.org/10.1038/jhg.2016.113
Benito-Sanz, Sara ; Belinchon-Martínez, Alberta ; Aza-Carmona, Miriam ; De La Torre, Carolina ; Huber, Celine ; González-Casado, Isabel ; Ross, Judith L. ; Thomas, N. Simon ; Zinn, Andrew R. ; Cormier-Daire, Valerie ; Heath, Karen E. / 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. In: Journal of Human Genetics. 2017 ; Vol. 62, No. 2. pp. 229-234.
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