SHOX gene defects and selected dysmorphic signs in patients of idiopathic short stature and Léri-Weill dyschondrosteosis
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22020182
DOI
10.1016/j.gene.2011.10.011
PII: S0378-1119(11)00586-5
Knihovny.cz E-resources
- MeSH
- Child MeSH
- Adult MeSH
- Homeodomain Proteins cerebrospinal fluid genetics MeSH
- Humans MeSH
- Adolescent MeSH
- Mutation * MeSH
- Osteochondrodysplasias diagnosis genetics MeSH
- Growth Disorders diagnosis genetics MeSH
- Child, Preschool MeSH
- Short Stature Homeobox Protein MeSH
- Muscular Atrophy genetics MeSH
- DNA Copy Number Variations MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Homeodomain Proteins MeSH
- Short Stature Homeobox Protein MeSH
- SHOX protein, human MeSH Browser
The aim of the study was to analyze frequency of SHOX gene defects and selected dysmorphic signs in patients of both idiopathic short stature (ISS) and Léri-Weill dyschondrosteosis (LWD), all derived from the Czech population. Overall, 98 subjects were analyzed in the study. Inclusion criteria were the presence of short stature (-2.0 SD), in combination with at least one of the selected dysmorphic signs for the ISS+ group; and the presence of Madelung deformity, without positive karyotyping for the LWD+ group. Each proband was analyzed by use of P018 MLPA kit, which covers SHOX and its regulatory sequences. Additionally, mutational analysis was done of the coding portions of the SHOX. Both extent and breakpoint localizations in the deletions/duplications found were quite variable. Some PAR1 rearrangements were detected, without obvious phenotypic association. In the ISS+ group, MLPA analysis detected four PAR1 deletions associated with a SHOX gene defect, PAR1 duplication with an ambiguous effect, and two SHOX mutations (13.7%). In the LWD+ group, MLPA analysis detected nine deletions in PAR1 region, with a deleterious effect on SHOX, first reported case of isolated SHOX enhancer duplication, and SHOX mutation (68.8%). In both ISS+ and LWD+ groups were positivity associated with a disproportionately short stature; in the ISS+ group, in combination with muscular hypertrophy. It seems that small PAR1 rearrangements might be quite frequent in the population. Our study suggests disproportionateness, especially in combination with muscular hypertrophy, as relevant indicators of ISS to be the effect of SHOX defect.
References provided by Crossref.org
Analysis of common SHOX gene sequence variants and ~4.9-kb PAR1 deletion in ISS patients
