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Phenotypic characterization of patients with deletions in the 3’-flanking SHOX region
Context. Leri–Weill dyschondrosteosis is a clinically variable skeletal dysplasia, caused by SHOX deletion or mutations, or a deletion of enhancer sequences in the 3’-flanking region. Recently, a 47.5 kb recurrent PAR1 deletion downstream of SHOX was reported, but its frequency and clinical importan...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629036/ https://www.ncbi.nlm.nih.gov/pubmed/23638371 http://dx.doi.org/10.7717/peerj.35 |
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author | Kant, Sarina G. Broekman, Sander J. de Wit, Caroline C. Bos, Marloes Scheltinga, Sitha A. Bakker, Egbert Oostdijk, Wilma van der Kamp, Hetty J. van Zwet, Erik W. van der Hout, Annemieke H. Wit, Jan M. Losekoot, Monique |
author_facet | Kant, Sarina G. Broekman, Sander J. de Wit, Caroline C. Bos, Marloes Scheltinga, Sitha A. Bakker, Egbert Oostdijk, Wilma van der Kamp, Hetty J. van Zwet, Erik W. van der Hout, Annemieke H. Wit, Jan M. Losekoot, Monique |
author_sort | Kant, Sarina G. |
collection | PubMed |
description | Context. Leri–Weill dyschondrosteosis is a clinically variable skeletal dysplasia, caused by SHOX deletion or mutations, or a deletion of enhancer sequences in the 3’-flanking region. Recently, a 47.5 kb recurrent PAR1 deletion downstream of SHOX was reported, but its frequency and clinical importance are still unknown. Objective. This study aims to compare the clinical features of different sizes of deletions in the 3’-flanking SHOX region in order to determine the relevance of the regulatory sequences in this region. Design. We collected DNA from 28 families with deletions in the 3’-PAR1 region. Clinical data were available from 23 index patients and 21 relatives. Results. In 9 families (20 individuals) a large deletion ( ∼ 200–900 kb) was found and in 19 families (35 individuals) a small deletion was demonstrated, equal to the recently described 47.5 kb PAR1 deletion. Median height SDS, sitting height/height ratio SDS and the presence of Madelung deformity in patients with the 47.5 kb deletion were not significantly different from patients with larger deletions. The index patients had a median height SDS which was slightly lower than in their affected family members (p = 0.08). No significant differences were observed between male and female patients. Conclusions. The phenotype of patients with deletions in the 3’-PAR1 region is remarkably variable. Height, sitting height/height ratio and the presence of Madelung deformity were not significantly different between patients with the 47.5 kb recurrent PAR1 deletion and those with larger deletions, suggesting that this enhancer plays an important role in SHOX expression. |
format | Online Article Text |
id | pubmed-3629036 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-36290362013-05-01 Phenotypic characterization of patients with deletions in the 3’-flanking SHOX region Kant, Sarina G. Broekman, Sander J. de Wit, Caroline C. Bos, Marloes Scheltinga, Sitha A. Bakker, Egbert Oostdijk, Wilma van der Kamp, Hetty J. van Zwet, Erik W. van der Hout, Annemieke H. Wit, Jan M. Losekoot, Monique Peerj Genetics Context. Leri–Weill dyschondrosteosis is a clinically variable skeletal dysplasia, caused by SHOX deletion or mutations, or a deletion of enhancer sequences in the 3’-flanking region. Recently, a 47.5 kb recurrent PAR1 deletion downstream of SHOX was reported, but its frequency and clinical importance are still unknown. Objective. This study aims to compare the clinical features of different sizes of deletions in the 3’-flanking SHOX region in order to determine the relevance of the regulatory sequences in this region. Design. We collected DNA from 28 families with deletions in the 3’-PAR1 region. Clinical data were available from 23 index patients and 21 relatives. Results. In 9 families (20 individuals) a large deletion ( ∼ 200–900 kb) was found and in 19 families (35 individuals) a small deletion was demonstrated, equal to the recently described 47.5 kb PAR1 deletion. Median height SDS, sitting height/height ratio SDS and the presence of Madelung deformity in patients with the 47.5 kb deletion were not significantly different from patients with larger deletions. The index patients had a median height SDS which was slightly lower than in their affected family members (p = 0.08). No significant differences were observed between male and female patients. Conclusions. The phenotype of patients with deletions in the 3’-PAR1 region is remarkably variable. Height, sitting height/height ratio and the presence of Madelung deformity were not significantly different between patients with the 47.5 kb recurrent PAR1 deletion and those with larger deletions, suggesting that this enhancer plays an important role in SHOX expression. PeerJ Inc. 2013-02-19 /pmc/articles/PMC3629036/ /pubmed/23638371 http://dx.doi.org/10.7717/peerj.35 Text en © 2013 Kant et al. http://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Genetics Kant, Sarina G. Broekman, Sander J. de Wit, Caroline C. Bos, Marloes Scheltinga, Sitha A. Bakker, Egbert Oostdijk, Wilma van der Kamp, Hetty J. van Zwet, Erik W. van der Hout, Annemieke H. Wit, Jan M. Losekoot, Monique Phenotypic characterization of patients with deletions in the 3’-flanking SHOX region |
title | Phenotypic characterization of patients with deletions in the 3’-flanking SHOX region |
title_full | Phenotypic characterization of patients with deletions in the 3’-flanking SHOX region |
title_fullStr | Phenotypic characterization of patients with deletions in the 3’-flanking SHOX region |
title_full_unstemmed | Phenotypic characterization of patients with deletions in the 3’-flanking SHOX region |
title_short | Phenotypic characterization of patients with deletions in the 3’-flanking SHOX region |
title_sort | phenotypic characterization of patients with deletions in the 3’-flanking shox region |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629036/ https://www.ncbi.nlm.nih.gov/pubmed/23638371 http://dx.doi.org/10.7717/peerj.35 |
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