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Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations

Axial spondylometaphyseal dysplasia (axial SMD) is an autosomal recessive disease characterized by dysplasia of axial skeleton and retinal dystrophy. We conducted whole exome sequencing and identified C21orf2 (chromosome 21 open reading frame 2) as a disease gene for axial SMD. C21orf2 mutations hav...

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Autores principales: Wang, Zheng, Iida, Aritoshi, Miyake, Noriko, Nishiguchi, Koji M., Fujita, Kosuke, Nakazawa, Toru, Alswaid, Abdulrahman, Albalwi, Mohammed A., Kim, Ok-Hwa, Cho, Tae-Joon, Lim, Gye-Yeon, Isidor, Bertrand, David, Albert, Rustad, Cecilie F., Merckoll, Else, Westvik, Jostein, Stattin, Eva-Lena, Grigelioniene, Giedre, Kou, Ikuyo, Nakajima, Masahiro, Ohashi, Hirohumi, Smithson, Sarah, Matsumoto, Naomichi, Nishimura, Gen, Ikegawa, Shiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790905/
https://www.ncbi.nlm.nih.gov/pubmed/26974433
http://dx.doi.org/10.1371/journal.pone.0150555
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author Wang, Zheng
Iida, Aritoshi
Miyake, Noriko
Nishiguchi, Koji M.
Fujita, Kosuke
Nakazawa, Toru
Alswaid, Abdulrahman
Albalwi, Mohammed A.
Kim, Ok-Hwa
Cho, Tae-Joon
Lim, Gye-Yeon
Isidor, Bertrand
David, Albert
Rustad, Cecilie F.
Merckoll, Else
Westvik, Jostein
Stattin, Eva-Lena
Grigelioniene, Giedre
Kou, Ikuyo
Nakajima, Masahiro
Ohashi, Hirohumi
Smithson, Sarah
Matsumoto, Naomichi
Nishimura, Gen
Ikegawa, Shiro
author_facet Wang, Zheng
Iida, Aritoshi
Miyake, Noriko
Nishiguchi, Koji M.
Fujita, Kosuke
Nakazawa, Toru
Alswaid, Abdulrahman
Albalwi, Mohammed A.
Kim, Ok-Hwa
Cho, Tae-Joon
Lim, Gye-Yeon
Isidor, Bertrand
David, Albert
Rustad, Cecilie F.
Merckoll, Else
Westvik, Jostein
Stattin, Eva-Lena
Grigelioniene, Giedre
Kou, Ikuyo
Nakajima, Masahiro
Ohashi, Hirohumi
Smithson, Sarah
Matsumoto, Naomichi
Nishimura, Gen
Ikegawa, Shiro
author_sort Wang, Zheng
collection PubMed
description Axial spondylometaphyseal dysplasia (axial SMD) is an autosomal recessive disease characterized by dysplasia of axial skeleton and retinal dystrophy. We conducted whole exome sequencing and identified C21orf2 (chromosome 21 open reading frame 2) as a disease gene for axial SMD. C21orf2 mutations have been recently found to cause isolated retinal degeneration and Jeune syndrome. We found a total of five biallelic C21orf2 mutations in six families out of nine: three missense and two splicing mutations in patients with various ethnic backgrounds. The pathogenic effects of the splicing (splice-site and branch-point) mutations were confirmed on RNA level, which showed complex patterns of abnormal splicing. C21orf2 mutations presented with a wide range of skeletal phenotypes, including cupped and flared anterior ends of ribs, lacy ilia and metaphyseal dysplasia of proximal femora. Analysis of patients without C21orf2 mutation indicated genetic heterogeneity of axial SMD. Functional data in chondrocyte suggest C21orf2 is implicated in cartilage differentiation. C21orf2 protein was localized to the connecting cilium of the cone and rod photoreceptors, confirming its significance in retinal function. Our study indicates that axial SMD is a member of a unique group of ciliopathy affecting skeleton and retina.
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spelling pubmed-47909052016-03-23 Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations Wang, Zheng Iida, Aritoshi Miyake, Noriko Nishiguchi, Koji M. Fujita, Kosuke Nakazawa, Toru Alswaid, Abdulrahman Albalwi, Mohammed A. Kim, Ok-Hwa Cho, Tae-Joon Lim, Gye-Yeon Isidor, Bertrand David, Albert Rustad, Cecilie F. Merckoll, Else Westvik, Jostein Stattin, Eva-Lena Grigelioniene, Giedre Kou, Ikuyo Nakajima, Masahiro Ohashi, Hirohumi Smithson, Sarah Matsumoto, Naomichi Nishimura, Gen Ikegawa, Shiro PLoS One Research Article Axial spondylometaphyseal dysplasia (axial SMD) is an autosomal recessive disease characterized by dysplasia of axial skeleton and retinal dystrophy. We conducted whole exome sequencing and identified C21orf2 (chromosome 21 open reading frame 2) as a disease gene for axial SMD. C21orf2 mutations have been recently found to cause isolated retinal degeneration and Jeune syndrome. We found a total of five biallelic C21orf2 mutations in six families out of nine: three missense and two splicing mutations in patients with various ethnic backgrounds. The pathogenic effects of the splicing (splice-site and branch-point) mutations were confirmed on RNA level, which showed complex patterns of abnormal splicing. C21orf2 mutations presented with a wide range of skeletal phenotypes, including cupped and flared anterior ends of ribs, lacy ilia and metaphyseal dysplasia of proximal femora. Analysis of patients without C21orf2 mutation indicated genetic heterogeneity of axial SMD. Functional data in chondrocyte suggest C21orf2 is implicated in cartilage differentiation. C21orf2 protein was localized to the connecting cilium of the cone and rod photoreceptors, confirming its significance in retinal function. Our study indicates that axial SMD is a member of a unique group of ciliopathy affecting skeleton and retina. Public Library of Science 2016-03-14 /pmc/articles/PMC4790905/ /pubmed/26974433 http://dx.doi.org/10.1371/journal.pone.0150555 Text en © 2016 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wang, Zheng
Iida, Aritoshi
Miyake, Noriko
Nishiguchi, Koji M.
Fujita, Kosuke
Nakazawa, Toru
Alswaid, Abdulrahman
Albalwi, Mohammed A.
Kim, Ok-Hwa
Cho, Tae-Joon
Lim, Gye-Yeon
Isidor, Bertrand
David, Albert
Rustad, Cecilie F.
Merckoll, Else
Westvik, Jostein
Stattin, Eva-Lena
Grigelioniene, Giedre
Kou, Ikuyo
Nakajima, Masahiro
Ohashi, Hirohumi
Smithson, Sarah
Matsumoto, Naomichi
Nishimura, Gen
Ikegawa, Shiro
Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations
title Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations
title_full Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations
title_fullStr Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations
title_full_unstemmed Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations
title_short Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations
title_sort axial spondylometaphyseal dysplasia is caused by c21orf2 mutations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790905/
https://www.ncbi.nlm.nih.gov/pubmed/26974433
http://dx.doi.org/10.1371/journal.pone.0150555
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