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A Novel Mutation c.3392G>T of COL2A1 Causes Spondyloepiphyseal Dysplasia Congenital by Affecting Pre-mRNA Splicing
Spondyloepiphyseal dysplasia congenital (SEDC) is a rare chondrodysplasia caused by dominant pathogenic variants in COL2A1. Here, we detected a novel variant c.3392G > T (NM_001844.4) of COL2A1 in a Chinese family with SEDC by targeted next-generation sequencing. To confirm the pathogenicity of t...
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/PMC9174977/ https://www.ncbi.nlm.nih.gov/pubmed/35692839 http://dx.doi.org/10.3389/fgene.2022.827560 |
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author | Fan, Lihong Ji, Longfei Xu, Yuqing Shen, Guosong Tang, Kefeng Li, Zhi Ye, Sisi Shen, Xueping |
author_facet | Fan, Lihong Ji, Longfei Xu, Yuqing Shen, Guosong Tang, Kefeng Li, Zhi Ye, Sisi Shen, Xueping |
author_sort | Fan, Lihong |
collection | PubMed |
description | Spondyloepiphyseal dysplasia congenital (SEDC) is a rare chondrodysplasia caused by dominant pathogenic variants in COL2A1. Here, we detected a novel variant c.3392G > T (NM_001844.4) of COL2A1 in a Chinese family with SEDC by targeted next-generation sequencing. To confirm the pathogenicity of the variant, we generated an appropriate minigene construct based on HeLa and HEK293T cell lines. Splicing assay indicated that the mutated minigene led to aberrant splicing of COL2A1 pre-mRNA and produced an alternatively spliced transcript with a skipping of partial exon 48, which generated a predicted in-frame deletion of 15 amino acids (p. Gly1131_Pro1145del) in the COL2A1 protein. Due to the pathogenicity of the variation, we performed prenatal diagnosis on the proband’s wife, which indicated that the fetus carried the same mutation. |
format | Online Article Text |
id | pubmed-9174977 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91749772022-06-09 A Novel Mutation c.3392G>T of COL2A1 Causes Spondyloepiphyseal Dysplasia Congenital by Affecting Pre-mRNA Splicing Fan, Lihong Ji, Longfei Xu, Yuqing Shen, Guosong Tang, Kefeng Li, Zhi Ye, Sisi Shen, Xueping Front Genet Genetics Spondyloepiphyseal dysplasia congenital (SEDC) is a rare chondrodysplasia caused by dominant pathogenic variants in COL2A1. Here, we detected a novel variant c.3392G > T (NM_001844.4) of COL2A1 in a Chinese family with SEDC by targeted next-generation sequencing. To confirm the pathogenicity of the variant, we generated an appropriate minigene construct based on HeLa and HEK293T cell lines. Splicing assay indicated that the mutated minigene led to aberrant splicing of COL2A1 pre-mRNA and produced an alternatively spliced transcript with a skipping of partial exon 48, which generated a predicted in-frame deletion of 15 amino acids (p. Gly1131_Pro1145del) in the COL2A1 protein. Due to the pathogenicity of the variation, we performed prenatal diagnosis on the proband’s wife, which indicated that the fetus carried the same mutation. Frontiers Media S.A. 2022-04-05 /pmc/articles/PMC9174977/ /pubmed/35692839 http://dx.doi.org/10.3389/fgene.2022.827560 Text en Copyright © 2022 Fan, Ji, Xu, Shen, Tang, Li, Ye and Shen. 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 Fan, Lihong Ji, Longfei Xu, Yuqing Shen, Guosong Tang, Kefeng Li, Zhi Ye, Sisi Shen, Xueping A Novel Mutation c.3392G>T of COL2A1 Causes Spondyloepiphyseal Dysplasia Congenital by Affecting Pre-mRNA Splicing |
title | A Novel Mutation c.3392G>T of COL2A1 Causes Spondyloepiphyseal Dysplasia Congenital by Affecting Pre-mRNA Splicing |
title_full | A Novel Mutation c.3392G>T of COL2A1 Causes Spondyloepiphyseal Dysplasia Congenital by Affecting Pre-mRNA Splicing |
title_fullStr | A Novel Mutation c.3392G>T of COL2A1 Causes Spondyloepiphyseal Dysplasia Congenital by Affecting Pre-mRNA Splicing |
title_full_unstemmed | A Novel Mutation c.3392G>T of COL2A1 Causes Spondyloepiphyseal Dysplasia Congenital by Affecting Pre-mRNA Splicing |
title_short | A Novel Mutation c.3392G>T of COL2A1 Causes Spondyloepiphyseal Dysplasia Congenital by Affecting Pre-mRNA Splicing |
title_sort | novel mutation c.3392g>t of col2a1 causes spondyloepiphyseal dysplasia congenital by affecting pre-mrna splicing |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174977/ https://www.ncbi.nlm.nih.gov/pubmed/35692839 http://dx.doi.org/10.3389/fgene.2022.827560 |
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