SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts
Autosomal recessive osteopetrosis (ARO) is a heterogeneous disorder, characterized by defective osteoclastic resorption of bone that results in increased bone density. We have studied nine individuals with an intermediate form of ARO, from the county of Västerbotten in Northern Sweden. All afflicted...
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ftpubmed:oai:pubmedcentral.nih.gov:5462793 2023-05-15T17:44:44+02:00 SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts Stattin, Eva-Lena Henning, Petra Klar, Joakim McDermott, Emma Stecksen-Blicks, Christina Sandström, Per-Erik Kellgren, Therese G. Rydén, Patrik Hallmans, Göran Lönnerholm, Torsten Ameur, Adam Helfrich, Miep H. Coxon, Fraser P. Dahl, Niklas Wikström, Johan Lerner, Ulf H. 2017-06-07 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462793/ https://doi.org/10.1038/s41598-017-02533-2 en eng Nature Publishing Group UK http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462793/ http://dx.doi.org/10.1038/s41598-017-02533-2 © 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/. CC-BY Article Text 2017 ftpubmed https://doi.org/10.1038/s41598-017-02533-2 2017-06-11T00:15:44Z Autosomal recessive osteopetrosis (ARO) is a heterogeneous disorder, characterized by defective osteoclastic resorption of bone that results in increased bone density. We have studied nine individuals with an intermediate form of ARO, from the county of Västerbotten in Northern Sweden. All afflicted individuals had an onset in early infancy with optic atrophy, and in four patients anemia was present at diagnosis. Tonsillar herniation, foramen magnum stenosis, and severe osteomyelitis of the jaw were common clinical features. Whole exome sequencing, verified by Sanger sequencing, identified a splice site mutation c.212 + 1 G > T in the SNX10 gene encoding sorting nexin 10. Sequence analysis of the SNX10 transcript in patients revealed activation of a cryptic splice site in intron 4 resulting in a frame shift and a premature stop (p.S66Nfs * 15). Haplotype analysis showed that all cases originated from a single mutational event, and the age of the mutation was estimated to be approximately 950 years. Functional analysis of osteoclast progenitors isolated from peripheral blood of patients revealed that stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL) resulted in a robust formation of large, multinucleated osteoclasts which generated sealing zones; however these osteoclasts exhibited defective ruffled borders and were unable to resorb bone in vitro. Text Northern Sweden PubMed Central (PMC) Scientific Reports 7 1 |
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Article Stattin, Eva-Lena Henning, Petra Klar, Joakim McDermott, Emma Stecksen-Blicks, Christina Sandström, Per-Erik Kellgren, Therese G. Rydén, Patrik Hallmans, Göran Lönnerholm, Torsten Ameur, Adam Helfrich, Miep H. Coxon, Fraser P. Dahl, Niklas Wikström, Johan Lerner, Ulf H. SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts |
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Autosomal recessive osteopetrosis (ARO) is a heterogeneous disorder, characterized by defective osteoclastic resorption of bone that results in increased bone density. We have studied nine individuals with an intermediate form of ARO, from the county of Västerbotten in Northern Sweden. All afflicted individuals had an onset in early infancy with optic atrophy, and in four patients anemia was present at diagnosis. Tonsillar herniation, foramen magnum stenosis, and severe osteomyelitis of the jaw were common clinical features. Whole exome sequencing, verified by Sanger sequencing, identified a splice site mutation c.212 + 1 G > T in the SNX10 gene encoding sorting nexin 10. Sequence analysis of the SNX10 transcript in patients revealed activation of a cryptic splice site in intron 4 resulting in a frame shift and a premature stop (p.S66Nfs * 15). Haplotype analysis showed that all cases originated from a single mutational event, and the age of the mutation was estimated to be approximately 950 years. Functional analysis of osteoclast progenitors isolated from peripheral blood of patients revealed that stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL) resulted in a robust formation of large, multinucleated osteoclasts which generated sealing zones; however these osteoclasts exhibited defective ruffled borders and were unable to resorb bone in vitro. |
format |
Text |
author |
Stattin, Eva-Lena Henning, Petra Klar, Joakim McDermott, Emma Stecksen-Blicks, Christina Sandström, Per-Erik Kellgren, Therese G. Rydén, Patrik Hallmans, Göran Lönnerholm, Torsten Ameur, Adam Helfrich, Miep H. Coxon, Fraser P. Dahl, Niklas Wikström, Johan Lerner, Ulf H. |
author_facet |
Stattin, Eva-Lena Henning, Petra Klar, Joakim McDermott, Emma Stecksen-Blicks, Christina Sandström, Per-Erik Kellgren, Therese G. Rydén, Patrik Hallmans, Göran Lönnerholm, Torsten Ameur, Adam Helfrich, Miep H. Coxon, Fraser P. Dahl, Niklas Wikström, Johan Lerner, Ulf H. |
author_sort |
Stattin, Eva-Lena |
title |
SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts |
title_short |
SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts |
title_full |
SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts |
title_fullStr |
SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts |
title_full_unstemmed |
SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts |
title_sort |
snx10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts |
publisher |
Nature Publishing Group UK |
publishDate |
2017 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462793/ https://doi.org/10.1038/s41598-017-02533-2 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462793/ http://dx.doi.org/10.1038/s41598-017-02533-2 |
op_rights |
© 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/. |
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CC-BY |
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https://doi.org/10.1038/s41598-017-02533-2 |
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