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A Null Mutation of TNFRSF11A Causes Dysosteosclerosis, Not Osteopetrosis
Dysosteosclerosis (DOS) is a rare sclerosing bone dysplasia characterized by unique osteosclerosis of the long tubular bones and platyspondyly. DOS is inherited in an autosomal recessive manner and is genetically and clinically heterogeneous. To date, four individuals with DOS who have five differen...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263543/ https://www.ncbi.nlm.nih.gov/pubmed/35812760 http://dx.doi.org/10.3389/fgene.2022.938814 |
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author | Kırkgöz, Tarık Özkan, Behzat Hazan, Filiz Acar, Sezer Nalbantoğlu, Özlem Özkaya, Beyhan Kulalı, Melike Ataseven Gürsoy, Semra Ikegawa, Shiro Guo, Long |
author_facet | Kırkgöz, Tarık Özkan, Behzat Hazan, Filiz Acar, Sezer Nalbantoğlu, Özlem Özkaya, Beyhan Kulalı, Melike Ataseven Gürsoy, Semra Ikegawa, Shiro Guo, Long |
author_sort | Kırkgöz, Tarık |
collection | PubMed |
description | Dysosteosclerosis (DOS) is a rare sclerosing bone dysplasia characterized by unique osteosclerosis of the long tubular bones and platyspondyly. DOS is inherited in an autosomal recessive manner and is genetically and clinically heterogeneous. To date, four individuals with DOS who have five different TNFRSF11A mutations have been reported. Based on their data, it is hypothesized that mutations producing aberrant mutant RANK proteins (missense or truncated or elongated) cause DOS, while null mutations lead to osteopetrosis, autosomal recessive 7 (OPTB7). Herein, we present the fifth case of TNFRSF11A-associated DOS with a novel homozygous frame-shift mutation (c.19_31del; p.[Arg7CysfsTer172]). The mutation is predicted to cause nonsense mutation-mediated mRNA decay (NMD) in all RANK isoform transcripts, resulting in totally null allele. Our findings suggest genotype-phenotype relationship in TNFRSF11A-associated OPTB7 and DOS remains unclear, and that the deficiency of TNFRSF11A functions might cause DOS, rather than osteopetrosis. More data are necessary to understand the phenotypic spectrum caused by TNFRSF11A mutations. |
format | Online Article Text |
id | pubmed-9263543 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92635432022-07-09 A Null Mutation of TNFRSF11A Causes Dysosteosclerosis, Not Osteopetrosis Kırkgöz, Tarık Özkan, Behzat Hazan, Filiz Acar, Sezer Nalbantoğlu, Özlem Özkaya, Beyhan Kulalı, Melike Ataseven Gürsoy, Semra Ikegawa, Shiro Guo, Long Front Genet Genetics Dysosteosclerosis (DOS) is a rare sclerosing bone dysplasia characterized by unique osteosclerosis of the long tubular bones and platyspondyly. DOS is inherited in an autosomal recessive manner and is genetically and clinically heterogeneous. To date, four individuals with DOS who have five different TNFRSF11A mutations have been reported. Based on their data, it is hypothesized that mutations producing aberrant mutant RANK proteins (missense or truncated or elongated) cause DOS, while null mutations lead to osteopetrosis, autosomal recessive 7 (OPTB7). Herein, we present the fifth case of TNFRSF11A-associated DOS with a novel homozygous frame-shift mutation (c.19_31del; p.[Arg7CysfsTer172]). The mutation is predicted to cause nonsense mutation-mediated mRNA decay (NMD) in all RANK isoform transcripts, resulting in totally null allele. Our findings suggest genotype-phenotype relationship in TNFRSF11A-associated OPTB7 and DOS remains unclear, and that the deficiency of TNFRSF11A functions might cause DOS, rather than osteopetrosis. More data are necessary to understand the phenotypic spectrum caused by TNFRSF11A mutations. Frontiers Media S.A. 2022-06-24 /pmc/articles/PMC9263543/ /pubmed/35812760 http://dx.doi.org/10.3389/fgene.2022.938814 Text en Copyright © 2022 Kırkgöz, Özkan, Hazan, Acar, Nalbantoğlu, Özkaya, Kulalı, Gürsoy, Ikegawa and Guo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Kırkgöz, Tarık Özkan, Behzat Hazan, Filiz Acar, Sezer Nalbantoğlu, Özlem Özkaya, Beyhan Kulalı, Melike Ataseven Gürsoy, Semra Ikegawa, Shiro Guo, Long A Null Mutation of TNFRSF11A Causes Dysosteosclerosis, Not Osteopetrosis |
title | A Null Mutation of TNFRSF11A Causes Dysosteosclerosis, Not Osteopetrosis |
title_full | A Null Mutation of TNFRSF11A Causes Dysosteosclerosis, Not Osteopetrosis |
title_fullStr | A Null Mutation of TNFRSF11A Causes Dysosteosclerosis, Not Osteopetrosis |
title_full_unstemmed | A Null Mutation of TNFRSF11A Causes Dysosteosclerosis, Not Osteopetrosis |
title_short | A Null Mutation of TNFRSF11A Causes Dysosteosclerosis, Not Osteopetrosis |
title_sort | null mutation of tnfrsf11a causes dysosteosclerosis, not osteopetrosis |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263543/ https://www.ncbi.nlm.nih.gov/pubmed/35812760 http://dx.doi.org/10.3389/fgene.2022.938814 |
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