title: Potentially Treatable Disorder Diagnosed Post Mortem by Exome Analysis in a Boy with Respiratory Distress.
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 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.
authors.affiliation: Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy. imperatore2@student.unisi.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Imperatore
authors.affiliation: Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy. mariaantonietta.mencarelli@unisi.it.|Genetica Medica, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy. mariaantonietta.mencarelli@unisi.it.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Mencarelli
authors.affiliation: Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy. fallerini2@unisi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fallerini
authors.affiliation: Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy. bianciardi19@unisi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Bianciardi
authors.affiliation: Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy. francesca.ariani@unisi.it.|Genetica Medica, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy. francesca.ariani@unisi.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ariani
authors.affiliation: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy. furini.simone@gmail.com.
authors.forename: Simone
authors.initials: S
authors.lastname: Furini
authors.affiliation: Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy. alessandra.renieri@unisi.it.|Genetica Medica, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy. alessandra.renieri@unisi.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
authors.affiliation: Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy. francesca.mari@unisi.it.|Genetica Medica, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy. francesca.mari@unisi.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mari
authors.affiliation: Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy. elisa.frullanti@dbm.unisi.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Frullanti
mesh_terms: D001344:Autopsy; D002648:Child; D059472:Exome; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D020125:Mutation, Missense; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics* / Q000473:pathology; D012120:Respiration Disorders / Q000235:genetics* / Q000473:pathology
chemical_list: D009124:Muscle Proteins; C051609:peripheral membrane protein 43K
keywords: complex disorder; exome sequencing; myasthenia; perinatal death