{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:41:51Z","timestamp":1760784111222,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2016,2,27]],"date-time":"2016-02-27T00:00:00Z","timestamp":1456531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms17030306","type":"journal-article","created":{"date-parts":[[2016,2,29]],"date-time":"2016-02-29T10:55:59Z","timestamp":1456743359000},"page":"306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Potentially Treatable Disorder Diagnosed Post Mortem by Exome Analysis in a Boy with Respiratory Distress"],"prefix":"10.3390","volume":"17","author":[{"given":"Valentina","family":"Imperatore","sequence":"first","affiliation":[{"name":"Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Mencarelli","sequence":"additional","affiliation":[{"name":"Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy"},{"name":"Genetica Medica, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Fallerini","sequence":"additional","affiliation":[{"name":"Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Bianciardi","sequence":"additional","affiliation":[{"name":"Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Ariani","sequence":"additional","affiliation":[{"name":"Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy"},{"name":"Genetica Medica, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Furini","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0846-9220","authenticated-orcid":false,"given":"Alessandra","family":"Renieri","sequence":"additional","affiliation":[{"name":"Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy"},{"name":"Genetica Medica, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1992-1654","authenticated-orcid":false,"given":"Francesca","family":"Mari","sequence":"additional","affiliation":[{"name":"Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy"},{"name":"Genetica Medica, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5634-031X","authenticated-orcid":false,"given":"Elisa","family":"Frullanti","sequence":"additional","affiliation":[{"name":"Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1056\/NEJMoa1306555","article-title":"Clinical whole-exome sequencing for the diagnosis of mendelian disorders","volume":"369","author":"Yang","year":"2013","journal-title":"N. 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