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Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies
The skeletal ciliopathies are a heterogeneous group of disorders with a significant clinical and genetic variability and the main clinical features are thoracic hypoplasia and short tubular bones. To date, 25 genes have been identified in association with skeletal ciliopathies. Mutations in the KIAA...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686170/ https://www.ncbi.nlm.nih.gov/pubmed/29138412 http://dx.doi.org/10.1038/s41598-017-15442-1 |
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author | Hammarsjö, A. Wang, Z. Vaz, R. Taylan, F. Sedghi, M. Girisha, K. M. Chitayat, D. Neethukrishna, K. Shannon, P. Godoy, R. Gowrishankar, K. Lindstrand, A. Nasiri, J. Baktashian, M. Newton, P. T. Guo, L. Hofmeister, W. Pettersson, M. Chagin, A. S. Nishimura, G. Yan, L. Matsumoto, N. Nordgren, A. Miyake, N. Grigelioniene, G. Ikegawa, S. |
author_facet | Hammarsjö, A. Wang, Z. Vaz, R. Taylan, F. Sedghi, M. Girisha, K. M. Chitayat, D. Neethukrishna, K. Shannon, P. Godoy, R. Gowrishankar, K. Lindstrand, A. Nasiri, J. Baktashian, M. Newton, P. T. Guo, L. Hofmeister, W. Pettersson, M. Chagin, A. S. Nishimura, G. Yan, L. Matsumoto, N. Nordgren, A. Miyake, N. Grigelioniene, G. Ikegawa, S. |
author_sort | Hammarsjö, A. |
collection | PubMed |
description | The skeletal ciliopathies are a heterogeneous group of disorders with a significant clinical and genetic variability and the main clinical features are thoracic hypoplasia and short tubular bones. To date, 25 genes have been identified in association with skeletal ciliopathies. Mutations in the KIAA0753 gene have recently been associated with Joubert syndrome (JBTS) and orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants in KIAA0753 in four patients with short-rib type skeletal dysplasia. The manifestations in our patients are variable and ranging from fetal lethal to viable and moderate skeletal dysplasia with narrow thorax and abnormal metaphyses. We demonstrate that KIAA0753 is expressed in normal fetal human growth plate and show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by our findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning. |
format | Online Article Text |
id | pubmed-5686170 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56861702017-11-21 Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies Hammarsjö, A. Wang, Z. Vaz, R. Taylan, F. Sedghi, M. Girisha, K. M. Chitayat, D. Neethukrishna, K. Shannon, P. Godoy, R. Gowrishankar, K. Lindstrand, A. Nasiri, J. Baktashian, M. Newton, P. T. Guo, L. Hofmeister, W. Pettersson, M. Chagin, A. S. Nishimura, G. Yan, L. Matsumoto, N. Nordgren, A. Miyake, N. Grigelioniene, G. Ikegawa, S. Sci Rep Article The skeletal ciliopathies are a heterogeneous group of disorders with a significant clinical and genetic variability and the main clinical features are thoracic hypoplasia and short tubular bones. To date, 25 genes have been identified in association with skeletal ciliopathies. Mutations in the KIAA0753 gene have recently been associated with Joubert syndrome (JBTS) and orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants in KIAA0753 in four patients with short-rib type skeletal dysplasia. The manifestations in our patients are variable and ranging from fetal lethal to viable and moderate skeletal dysplasia with narrow thorax and abnormal metaphyses. We demonstrate that KIAA0753 is expressed in normal fetal human growth plate and show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by our findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning. Nature Publishing Group UK 2017-11-14 /pmc/articles/PMC5686170/ /pubmed/29138412 http://dx.doi.org/10.1038/s41598-017-15442-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hammarsjö, A. Wang, Z. Vaz, R. Taylan, F. Sedghi, M. Girisha, K. M. Chitayat, D. Neethukrishna, K. Shannon, P. Godoy, R. Gowrishankar, K. Lindstrand, A. Nasiri, J. Baktashian, M. Newton, P. T. Guo, L. Hofmeister, W. Pettersson, M. Chagin, A. S. Nishimura, G. Yan, L. Matsumoto, N. Nordgren, A. Miyake, N. Grigelioniene, G. Ikegawa, S. Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies |
title | Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies |
title_full | Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies |
title_fullStr | Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies |
title_full_unstemmed | Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies |
title_short | Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies |
title_sort | novel kiaa0753 mutations extend the phenotype of skeletal ciliopathies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686170/ https://www.ncbi.nlm.nih.gov/pubmed/29138412 http://dx.doi.org/10.1038/s41598-017-15442-1 |
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