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 a7 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.

IMPERATORE, V., MENCARELLI, M.A., FALLERINI, C., BIANCIARDI, L., ARIANI, F., FURINI, S., et al. (2016). Potentially treatable disorder diagnosed post Mortem by exome analysis in a boy with respiratory distress. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 17(3), 306 [10.3390/ijms17030306].

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
2016

Abstract

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 a7 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.
IMPERATORE, V., MENCARELLI, M.A., FALLERINI, C., BIANCIARDI, L., ARIANI, F., FURINI, S., et al. (2016). Potentially treatable disorder diagnosed post Mortem by exome analysis in a boy with respiratory distress. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 17(3), 306 [10.3390/ijms17030306].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/996022
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