Léri-Weill Dyschondrosteosis



This SALSA MLPA probemix P018 SHOX is a research use only (RUO) assay for the detection of exon deletions or duplications in the human SHOX gene and a number of (putative) SHOX enhancer sequences and is not intended to be used as a standalone assay for clinical decisions. Most defects in the SHOX gene are point mutations, the majority of which will not be detected by MLPA. It is therefore recommended to use this SALSA MLPA probemix in combination with sequence analysis. Clinical background: Léri-Weill Dyschondrosteosis (LWD) is a dominant skeletal disorder characterised by short stature and distinct bone anomalies. Heterozygous deletions of the SHOX gene and/or regulatory elements downstream of SHOX, are detected in approximately 60% of LWD patients (Benito-Sanz et al. 2006; Huber et al. 2006; Fukami et al. 2006; Chen et al. 2009). The more severe form, Langer Mesomelic Dysplasia (LMD), is a result of (partial) inactivation of both SHOX copies. The SHOX gene and the regulatory elements downstream of SHOX, are located within the PAR1 region (pseudoautosomal region 1) which covers the first 3000 kb of the X and Y chromosomes next to the p-telomere. More information is available on http://www.ncbi.nlm.nih.gov/books/NBK1215/ Among the various defects in the SHOX gene that have been found in patients are deletions and duplications of complete exons, which are usually missed by standard sequence analysis. The MLPA technique can detect most of these deletions and duplications and therefore complements sequence analysis of the SHOX gene. The expected number of SHOX chromosomal rearrangements that can be detected with this MLPA probemix is between 35 and 70% of all SHOX mutations in most populations (Wolters et al, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1215/). See below for the publications on probemix P018 SHOX. P018-G1 probemix content: This SALSA MLPA probemix P018 SHOX contains 48 MLPA probes with amplification products between 124 and 502 nt: 27 probes for the SHOX gene region, 12 probes elsewhere on the X-chromosome (Table 2) and 9 reference probes. One probe is present for each exon of the human SHOX gene, as well as a probe just before the SHOX promoter region. In addition, several probes are present detecting sequences in regions upstream or downstream of SHOX which have been implicated in regulation of SHOX transcription. Furthermore, several probes on the X chromosome are included in this probemix that can be used to characterise larger deletions and to distinguish SHOX deletions from a Turner syndrome karyotype