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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Uppsala universitet, Science for Life Laboratory, SciLifeLab
2017
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ftuppsalauniv:oai:DiVA.org:uu-325569 2023-05-15T17:44:44+02:00 SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts. Stattin, Evalena 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 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-325569 https://doi.org/10.1038/s41598-017-02533-2 eng eng Uppsala universitet, Science for Life Laboratory, SciLifeLab Uppsala universitet, Institutionen för immunologi, genetik och patologi Uppsala universitet, Radiologi Umea Univ, Dept Med Biosci Med & Clin Genet, S-90187 Umea, Sweden Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr,Inst Med, S-40530 Gothenburg, Sweden Univ Aberdeen, Arthritis & Musculoskeletal Med Programme, Inst Med Sci, Aberdeen AB25 2ZD, Scotland Umea Univ, Pediat Dent, Dept Odontol, Fac Med, S-90187 Umea, Sweden Umea Univ, Dept Pediat, S-90187 Umea, Sweden Umea Univ, Dept Math & Math Stat, Computat Life Sci Cluster CLiC, S-90187 Umea, Sweden Umea Univ, Dept Biobank Res, S-90187 Umea, Sweden Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr,Inst Med, S-40530 Gothenburg, Sweden.; Umea Univ, Mol Periodontol, Dept Odontol, Fac Med, S-90187 Umea, Sweden Scientific Reports, 2017, 7, orcid:0000-0003-4185-7409 orcid:0000-0001-6085-6749 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-325569 doi:10.1038/s41598-017-02533-2 PMID 28592808 ISI:000402879800068 info:eu-repo/semantics/openAccess Medical and Health Sciences Medicin och hälsovetenskap Article in journal info:eu-repo/semantics/article text 2017 ftuppsalauniv https://doi.org/10.1038/s41598-017-02533-2 2023-02-23T22:00:28Z 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. Article in Journal/Newspaper Northern Sweden Uppsala University: Publications (DiVA) Scientific Reports 7 1 |
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Uppsala University: Publications (DiVA) |
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ftuppsalauniv |
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English |
topic |
Medical and Health Sciences Medicin och hälsovetenskap |
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Medical and Health Sciences Medicin och hälsovetenskap Stattin, Evalena 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. |
topic_facet |
Medical and Health Sciences Medicin och hälsovetenskap |
description |
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 |
Article in Journal/Newspaper |
author |
Stattin, Evalena 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, Evalena 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, Evalena |
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 |
Uppsala universitet, Science for Life Laboratory, SciLifeLab |
publishDate |
2017 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-325569 https://doi.org/10.1038/s41598-017-02533-2 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Scientific Reports, 2017, 7, orcid:0000-0003-4185-7409 orcid:0000-0001-6085-6749 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-325569 doi:10.1038/s41598-017-02533-2 PMID 28592808 ISI:000402879800068 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1038/s41598-017-02533-2 |
container_title |
Scientific Reports |
container_volume |
7 |
container_issue |
1 |
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1766147007582306304 |