Detection of SHOX gene aberrations in routine diagnostic practice and evaluation of phenotype scoring form effectiveness
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
PubMed
27708272
DOI
10.1038/jhg.2016.117
PII: jhg2016117
Knihovny.cz E-resources
- MeSH
- Gene Duplication genetics MeSH
- Phenotype MeSH
- Genetic Testing MeSH
- Homeodomain Proteins genetics MeSH
- Humans MeSH
- Multiplex Polymerase Chain Reaction MeSH
- DNA Mutational Analysis methods MeSH
- Dwarfism genetics MeSH
- Osteochondrodysplasias diagnosis genetics MeSH
- Growth Disorders diagnosis genetics MeSH
- Short Stature Homeobox Protein MeSH
- Retrospective Studies MeSH
- Sequence Deletion genetics MeSH
- Nucleic Acid Amplification Techniques MeSH
- Body Height genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Homeodomain Proteins MeSH
- Short Stature Homeobox Protein MeSH
- SHOX protein, human MeSH Browser
Heterozygous aberrations of SHOX gene have been reported to be responsible for Léri-Weill dyschondrosteosis (LWD) and small portion of idiopathic short stature. The study was established to assess effectiveness of using phenotype 'scoring form' in patients indicated for SHOX gene defect analysis. The submitted study is based on a retrospective group of 352 unrelated patients enrolled as a part of the routine diagnostic practice and analyzed for aberrations affecting the SHOX gene. All participants were scanned for deletion/duplication within the main pseudoautosomal region (PAR1) using the multiplex ligation-dependent probe amplification (MLPA) method. The phenotype 'scoring form' is used in our laboratory practice to preselect patients for subsequent mutation analysis of SHOX gene-coding sequences. The overall detection rate was 11.1% but there was a significant increase in frequency of SHOX gene defect positive with increasing achieved score (P<0.0001). The most frequent aberration was a causal deletion within PAR1. In three probands, MLPA analysis indicated a more complex rearrangement. Madelung deformity or co-occurrence of disproportionate short stature, short forearm and muscular hypertrophy had represented the most potent markers to determine the likelihood of SHOX gene defect detection. We conclude that appliance of phenotype 'scoring form' had saved excessive sample analysis and enabled effective routine diagnostic testing.
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