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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...

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Autores principales: Imperatore, Valentina, Mencarelli, Maria Antonietta, Fallerini, Chiara, Bianciardi, Laura, Ariani, Francesca, Furini, Simone, Renieri, Alessandra, Mari, Francesca, Frullanti, Elisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
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.
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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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