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SALSA MLPA KIT P262 Growth Hormone Insensitivity
[http://www.geneclinics.org/profiles/hht/details.html]
Growth hormone insensitivity (GHI) is characterized by severe short stature, normal to elevated serum levels of growth hormone (GH) and resistance to exogenous GH therapy. The etiology of GHI is classically associated with mutations in the GH receptor (GHR) gene or with mutations affecting the signaling cascade of the GHR. Intracellular signaling molecules activated by GH belong to the Janus kinase-signal transducer and activator of transcription 5b (JAK2-STAT5b) pathway. Amongst others, this pathway activates the insulin-like growth factor (IGF1), which is implicated in the regulation of protein turnover and exerts potent mitogenic and differentiating effects on most cell types. The GHR gene contains 10 exons and spans 297.9 kb on chromosome 5p12. There are 2 isoforms of GHR in humans, differing in the retention or exclusion of exon 3 during splicing: a full-length isoform (GHRfl) and an isoform lacking exon 3 (GHRd3). These isoforms present a widespread distribution in humans, with the frequency of each allele ranging from 68-75% for GHRfl and 25-32% for GHRd3 (Pantel J. et al. 2000). Growth hormone is used to increase height in short children who are not deficient in growth hormone receptor, but its efficacy varies widely across individuals. Dos Santos et al. (2004) found that the GHRd3 isoform was associated with 1.7 to 2 times more growth acceleration induced by growth hormone than the full-length isoform (P less than 0.0001). This probemix includes one probe for each GHR exon and an additional one for exon 10. The gene encoding IGF1 is situated on 12q23.2; it has 4 exons and is about 84.7 kb long. The P262 probemix includes one probe for each exon. Gene JAK2 comprises 25 exons, spans about 142.8 kb of genomic DNA and is located on 9q24.1. The P262 probemix includes 15 JAK2 probes for 15 different exons. In addition, the P262 probemix contains 12 probes detecting most of the 19 exons of the 77 kb long STAT5B gene which is located on chromosome 17q21.2. The SALSA MLPA kit P262 is designed to detect deletions/duplications of one or more exons of the GHR, IGF1, JAK2 and STAT5B genes. Deletions of probe recognition sequences will be apparent by a 35-50% reduced relative peak area of the amplification product of that probe. However, mutations/polymorphisms very close to the probe ligation site may also result in a reduced relative peak area. Apparent deletions of a single exon therefore always require confirmation by other methods. We have no information on what percentage of defects in these genes is caused by deletions/duplications of complete exons. Please note that most defects in these genes are expected to be small (point) mutations, most of which will not be detected by this MLPA test.
Full mix description (pdf)
IMPORTANT NOTICE: MLPA kits are sold by MRC-Holland for research purposes and to demonstrate the possibilities of the MLPA technique. This kit is not CE/FDA certified for use in diagnostic procedures. Salsa MLPA kits are supplied with all necessary buffers and enzymes. Purchase of the Salsa MLPA test kits includes a limited license to use these products for research purposes. The use of this MLPA kit requires a thermocycler with heated lid and sequence type electrophoresis equipment. Different fluorescent PCR primers are available. The MLPA technique has been first described in Nucleic Acid Research 30, e57 (2002)
References
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Last change in probemix content Current lot number
: lot 1007 : lot 1007
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