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

Overview

Journal J Hum Genet

Specialty Genetics

Date 2016 Sep 9

PMID 27604558

Citations 5

Authors

Sara Benito-Sanz

Alberta Belinchon-Martinez

Miriam Aza-Carmona

Carolina de la Torre

Celine Huber

Isabel Gonzalez-Casado

Judith L Ross

N Simon Thomas

Andrew R Zinn

Valerie Cormier-Daire

Karen E Heath

Affiliations

Soon will be listed here.

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.

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