Cargando…
A Novel Splicing Variant of COL2A1 in a Fetus with Achondrogenesis Type II: Interpretation of Pathogenicity of In-Frame Deletions
Achondrogenesis type II (ACG2) is a lethal skeletal dysplasia caused by dominant pathogenic variants in COL2A1. Most of the variants found in patients with ACG2 affect the glycine residue included in the Gly-X-Y tripeptide repeat that characterizes the type II collagen helix. In this study, we repor...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467821/ https://www.ncbi.nlm.nih.gov/pubmed/34573377 http://dx.doi.org/10.3390/genes12091395 |
_version_ | 1784573498716323840 |
---|---|
author | Bruni, Valentina Spoleti, Cristina Barbara La Barbera, Andrea Dattilo, Vincenzo Colao, Emma Votino, Carmela Bellacchio, Emanuele Perrotti, Nicola Giglio, Sabrina Iuliano, Rodolfo |
author_facet | Bruni, Valentina Spoleti, Cristina Barbara La Barbera, Andrea Dattilo, Vincenzo Colao, Emma Votino, Carmela Bellacchio, Emanuele Perrotti, Nicola Giglio, Sabrina Iuliano, Rodolfo |
author_sort | Bruni, Valentina |
collection | PubMed |
description | Achondrogenesis type II (ACG2) is a lethal skeletal dysplasia caused by dominant pathogenic variants in COL2A1. Most of the variants found in patients with ACG2 affect the glycine residue included in the Gly-X-Y tripeptide repeat that characterizes the type II collagen helix. In this study, we reported a case of a novel splicing variant of COL2A1 in a fetus with ACG2. An NGS analysis of fetal DNA revealed a heterozygous variant c.1267-2_1269del located in intron 20/exon 21. The variant occurred de novo since it was not detected in DNA from the blood samples of parents. We generated an appropriate minigene construct to study the effect of the variant detected. The minigene expression resulted in the synthesis of a COL2A1 messenger RNA lacking exon 21, which generated a predicted in-frame deleted protein. Usually, in-frame deletion variants of COL2A1 cause a phenotype such as Kniest dysplasia, which is milder than ACG2. Therefore, we propose that the size and position of an in-frame deletion in COL2A1 may be relevant in determining the phenotype of skeletal dysplasia. |
format | Online Article Text |
id | pubmed-8467821 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84678212021-09-27 A Novel Splicing Variant of COL2A1 in a Fetus with Achondrogenesis Type II: Interpretation of Pathogenicity of In-Frame Deletions Bruni, Valentina Spoleti, Cristina Barbara La Barbera, Andrea Dattilo, Vincenzo Colao, Emma Votino, Carmela Bellacchio, Emanuele Perrotti, Nicola Giglio, Sabrina Iuliano, Rodolfo Genes (Basel) Article Achondrogenesis type II (ACG2) is a lethal skeletal dysplasia caused by dominant pathogenic variants in COL2A1. Most of the variants found in patients with ACG2 affect the glycine residue included in the Gly-X-Y tripeptide repeat that characterizes the type II collagen helix. In this study, we reported a case of a novel splicing variant of COL2A1 in a fetus with ACG2. An NGS analysis of fetal DNA revealed a heterozygous variant c.1267-2_1269del located in intron 20/exon 21. The variant occurred de novo since it was not detected in DNA from the blood samples of parents. We generated an appropriate minigene construct to study the effect of the variant detected. The minigene expression resulted in the synthesis of a COL2A1 messenger RNA lacking exon 21, which generated a predicted in-frame deleted protein. Usually, in-frame deletion variants of COL2A1 cause a phenotype such as Kniest dysplasia, which is milder than ACG2. Therefore, we propose that the size and position of an in-frame deletion in COL2A1 may be relevant in determining the phenotype of skeletal dysplasia. MDPI 2021-09-10 /pmc/articles/PMC8467821/ /pubmed/34573377 http://dx.doi.org/10.3390/genes12091395 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bruni, Valentina Spoleti, Cristina Barbara La Barbera, Andrea Dattilo, Vincenzo Colao, Emma Votino, Carmela Bellacchio, Emanuele Perrotti, Nicola Giglio, Sabrina Iuliano, Rodolfo A Novel Splicing Variant of COL2A1 in a Fetus with Achondrogenesis Type II: Interpretation of Pathogenicity of In-Frame Deletions |
title | A Novel Splicing Variant of COL2A1 in a Fetus with Achondrogenesis Type II: Interpretation of Pathogenicity of In-Frame Deletions |
title_full | A Novel Splicing Variant of COL2A1 in a Fetus with Achondrogenesis Type II: Interpretation of Pathogenicity of In-Frame Deletions |
title_fullStr | A Novel Splicing Variant of COL2A1 in a Fetus with Achondrogenesis Type II: Interpretation of Pathogenicity of In-Frame Deletions |
title_full_unstemmed | A Novel Splicing Variant of COL2A1 in a Fetus with Achondrogenesis Type II: Interpretation of Pathogenicity of In-Frame Deletions |
title_short | A Novel Splicing Variant of COL2A1 in a Fetus with Achondrogenesis Type II: Interpretation of Pathogenicity of In-Frame Deletions |
title_sort | novel splicing variant of col2a1 in a fetus with achondrogenesis type ii: interpretation of pathogenicity of in-frame deletions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467821/ https://www.ncbi.nlm.nih.gov/pubmed/34573377 http://dx.doi.org/10.3390/genes12091395 |
work_keys_str_mv | AT brunivalentina anovelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT spoleticristinabarbara anovelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT labarberaandrea anovelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT dattilovincenzo anovelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT colaoemma anovelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT votinocarmela anovelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT bellacchioemanuele anovelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT perrottinicola anovelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT gigliosabrina anovelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT iulianorodolfo anovelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT brunivalentina novelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT spoleticristinabarbara novelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT labarberaandrea novelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT dattilovincenzo novelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT colaoemma novelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT votinocarmela novelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT bellacchioemanuele novelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT perrottinicola novelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT gigliosabrina novelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions AT iulianorodolfo novelsplicingvariantofcol2a1inafetuswithachondrogenesistypeiiinterpretationofpathogenicityofinframedeletions |