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Potentially Treatable Disorder Diagnosed Post Mortem by Exome Analysis in a Boy with Respiratory Distress
We highlight the importance of exome sequencing in solving a clinical case of a child who died at 14 months after a series of respiratory crises. He was the half-brother of a girl diagnosed at 7 years with the early-onset seizure variant of Rett syndrome due to CDKL5 mutation. We performed a test fo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813169/ https://www.ncbi.nlm.nih.gov/pubmed/26927095 http://dx.doi.org/10.3390/ijms17030306 |
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author | Imperatore, Valentina Mencarelli, Maria Antonietta Fallerini, Chiara Bianciardi, Laura Ariani, Francesca Furini, Simone Renieri, Alessandra Mari, Francesca Frullanti, Elisa |
author_facet | Imperatore, Valentina Mencarelli, Maria Antonietta Fallerini, Chiara Bianciardi, Laura Ariani, Francesca Furini, Simone Renieri, Alessandra Mari, Francesca Frullanti, Elisa |
author_sort | Imperatore, Valentina |
collection | PubMed |
description | We highlight the importance of exome sequencing in solving a clinical case of a child who died at 14 months after a series of respiratory crises. He was the half-brother of a girl diagnosed at 7 years with the early-onset seizure variant of Rett syndrome due to CDKL5 mutation. We performed a test for CDKL5 in the boy, which came back negative. Driven by the mother’s compelling need for a diagnosis, we moved forward performing whole exome sequencing analysis. Surprisingly, two missense mutations in compound heterozygosity were identified in the RAPSN gene encoding a receptor-associated protein with a key role in clustering and anchoring nicotinic acetylcholine receptors at synaptic sites. This gene is responsible for a congenital form of myasthenic syndrome, a disease potentially treatable with cholinesterase inhibitors. Therefore, an earlier diagnosis in this boy would have led to a better clinical management and prognosis. Our study supports the key role of exome sequencing in achieving a definite diagnosis in severe perinatal diseases, an essential step especially when a specific therapy is available. |
format | Online Article Text |
id | pubmed-4813169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-48131692016-04-06 Potentially Treatable Disorder Diagnosed Post Mortem by Exome Analysis in a Boy with Respiratory Distress Imperatore, Valentina Mencarelli, Maria Antonietta Fallerini, Chiara Bianciardi, Laura Ariani, Francesca Furini, Simone Renieri, Alessandra Mari, Francesca Frullanti, Elisa Int J Mol Sci Article We highlight the importance of exome sequencing in solving a clinical case of a child who died at 14 months after a series of respiratory crises. He was the half-brother of a girl diagnosed at 7 years with the early-onset seizure variant of Rett syndrome due to CDKL5 mutation. We performed a test for CDKL5 in the boy, which came back negative. Driven by the mother’s compelling need for a diagnosis, we moved forward performing whole exome sequencing analysis. Surprisingly, two missense mutations in compound heterozygosity were identified in the RAPSN gene encoding a receptor-associated protein with a key role in clustering and anchoring nicotinic acetylcholine receptors at synaptic sites. This gene is responsible for a congenital form of myasthenic syndrome, a disease potentially treatable with cholinesterase inhibitors. Therefore, an earlier diagnosis in this boy would have led to a better clinical management and prognosis. Our study supports the key role of exome sequencing in achieving a definite diagnosis in severe perinatal diseases, an essential step especially when a specific therapy is available. MDPI 2016-02-27 /pmc/articles/PMC4813169/ /pubmed/26927095 http://dx.doi.org/10.3390/ijms17030306 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Imperatore, Valentina Mencarelli, Maria Antonietta Fallerini, Chiara Bianciardi, Laura Ariani, Francesca Furini, Simone Renieri, Alessandra Mari, Francesca Frullanti, Elisa Potentially Treatable Disorder Diagnosed Post Mortem by Exome Analysis in a Boy with Respiratory Distress |
title | Potentially Treatable Disorder Diagnosed Post Mortem by Exome Analysis in a Boy with Respiratory Distress |
title_full | Potentially Treatable Disorder Diagnosed Post Mortem by Exome Analysis in a Boy with Respiratory Distress |
title_fullStr | Potentially Treatable Disorder Diagnosed Post Mortem by Exome Analysis in a Boy with Respiratory Distress |
title_full_unstemmed | Potentially Treatable Disorder Diagnosed Post Mortem by Exome Analysis in a Boy with Respiratory Distress |
title_short | Potentially Treatable Disorder Diagnosed Post Mortem by Exome Analysis in a Boy with Respiratory Distress |
title_sort | potentially treatable disorder diagnosed post mortem by exome analysis in a boy with respiratory distress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813169/ https://www.ncbi.nlm.nih.gov/pubmed/26927095 http://dx.doi.org/10.3390/ijms17030306 |
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