Cargando…
A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing
Pathogenic variants in non-coding regions of genes encoding enzymes or transporters of the urea cycle can lead to urea cycle disorders (UCDs). However, not all commercially available testing platforms interrogate these regions. Here, we used a gene panel based on massively parallel sequencing (MPS)...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809430/ https://www.ncbi.nlm.nih.gov/pubmed/33489762 http://dx.doi.org/10.1016/j.ymgmr.2020.100706 |
_version_ | 1783637120465764352 |
---|---|
author | Kumar, Runjun D. Burrage, Lindsay C. Bartos, Jan Ali, Saima Schmitt, Eric Nagamani, Sandesh C.S. LeMons, Cynthia |
author_facet | Kumar, Runjun D. Burrage, Lindsay C. Bartos, Jan Ali, Saima Schmitt, Eric Nagamani, Sandesh C.S. LeMons, Cynthia |
author_sort | Kumar, Runjun D. |
collection | PubMed |
description | Pathogenic variants in non-coding regions of genes encoding enzymes or transporters of the urea cycle can lead to urea cycle disorders (UCDs). However, not all commercially available testing platforms interrogate these regions. Here, we used a gene panel based on massively parallel sequencing (MPS) in 10 individuals with clinical or pedigree-based evidence of a proximal UCD but without a molecular confirmation of the diagnosis. We identified causal variant(s) in 5 of 10 individuals, including in 3 of 7 individuals in whom prior molecular testing was unrevealing. We show that a deep-intronic pathogenic variant in OTC, c.540+265G>A, is an important cause of ornithine transcarbamylase (OTC) deficiency. |
format | Online Article Text |
id | pubmed-7809430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-78094302021-01-22 A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing Kumar, Runjun D. Burrage, Lindsay C. Bartos, Jan Ali, Saima Schmitt, Eric Nagamani, Sandesh C.S. LeMons, Cynthia Mol Genet Metab Rep Short Communication Pathogenic variants in non-coding regions of genes encoding enzymes or transporters of the urea cycle can lead to urea cycle disorders (UCDs). However, not all commercially available testing platforms interrogate these regions. Here, we used a gene panel based on massively parallel sequencing (MPS) in 10 individuals with clinical or pedigree-based evidence of a proximal UCD but without a molecular confirmation of the diagnosis. We identified causal variant(s) in 5 of 10 individuals, including in 3 of 7 individuals in whom prior molecular testing was unrevealing. We show that a deep-intronic pathogenic variant in OTC, c.540+265G>A, is an important cause of ornithine transcarbamylase (OTC) deficiency. Elsevier 2021-01-08 /pmc/articles/PMC7809430/ /pubmed/33489762 http://dx.doi.org/10.1016/j.ymgmr.2020.100706 Text en © 2021 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Short Communication Kumar, Runjun D. Burrage, Lindsay C. Bartos, Jan Ali, Saima Schmitt, Eric Nagamani, Sandesh C.S. LeMons, Cynthia A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing |
title | A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing |
title_full | A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing |
title_fullStr | A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing |
title_full_unstemmed | A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing |
title_short | A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing |
title_sort | deep intronic variant is a common cause of otc deficiency in individuals with previously negative genetic testing |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809430/ https://www.ncbi.nlm.nih.gov/pubmed/33489762 http://dx.doi.org/10.1016/j.ymgmr.2020.100706 |
work_keys_str_mv | AT kumarrunjund adeepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT burragelindsayc adeepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT bartosjan adeepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT alisaima adeepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT schmitteric adeepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT nagamanisandeshcs adeepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT lemonscynthia adeepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT kumarrunjund deepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT burragelindsayc deepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT bartosjan deepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT alisaima deepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT schmitteric deepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT nagamanisandeshcs deepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting AT lemonscynthia deepintronicvariantisacommoncauseofotcdeficiencyinindividualswithpreviouslynegativegenetictesting |