@article {676,
	title = {Pathogenic Variants in NUP214 Cause "Plugged" Nuclear Pore Channels and Acute Febrile Encephalopathy.},
	journal = {Am J Hum Genet},
	volume = {105},
	year = {2019},
	month = {2019 Jul 03},
	pages = {48-64},
	abstract = {<p>We report biallelic missense and frameshift pathogenic variants in the gene encoding human nucleoporin NUP214 causing acute febrile encephalopathy. Clinical symptoms include neurodevelopmental regression, seizures, myoclonic jerks, progressive microcephaly, and cerebellar atrophy. NUP214 and NUP88 protein levels were reduced in primary skin fibroblasts derived from affected individuals, while the total number and density of nuclear pore complexes remained normal. Nuclear transport assays exhibited defects in the classical protein import and mRNA export pathways in affected cells. Direct surface imaging of fibroblast nuclei by scanning electron microscopy revealed a large increase in the presence of central particles (known as "plugs") in the nuclear pore channels of affected cells. This observation suggests that large transport cargoes may be delayed in passage through the nuclear pore channel, affecting its selective barrier function. Exposure of fibroblasts from affected individuals to heat shock resulted in a marked delay in their stress response, followed by a surge in apoptotic cell death. This suggests a mechanistic link between decreased cell survival in cell culture and severe fever-induced brain damage in affected individuals. Our study provides evidence by direct imaging at the single nuclear pore level of functional changes linked to a human disease.</p>},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2019.05.003},
	author = {Fichtman, Boris and Harel, Tamar and Biran, Nitzan and Zagairy, Fadia and Applegate, Carolyn D and Salzberg, Yuval and Gilboa, Tal and Salah, Somaya and Shaag, Avraham and Simanovsky, Natalia and Ayoubieh, Houriya and Sobreira, Nara and Punzi, Giuseppe and Pierri, Ciro Leonardo and Hamosh, Ada and Elpeleg, Orly and Harel, Amnon and Edvardson, Simon}
}
@article {310,
	title = {PhenoDB: a new web-based tool for the collection, storage, and analysis of phenotypic features.},
	journal = {Hum Mutat},
	volume = {34},
	year = {2013},
	month = {2013 Apr},
	pages = {566-71},
	abstract = {<p>To interpret whole exome/genome sequence data for clinical and research purposes, comprehensive phenotypic information, knowledge of pedigree structure, and results of previous clinical testing are essential. With these requirements in mind and to meet the needs of the Centers for Mendelian Genomics project, we have developed PhenoDB (http://phenodb.net), a secure, Web-based portal for entry, storage, and analysis of phenotypic and other clinical information. The phenotypic features are organized hierarchically according to the major headings and subheadings of the Online Mendelian Inheritance in Man (OMIM{\textregistered}) clinical synopses, with further subdivisions according to structure and function. Every string allows for a free-text entry. All of the approximately 2,900 features use the preferred term from Elements of Morphology and are fully searchable and mapped to the Human Phenotype Ontology and Elements of Morphology. The PhenoDB allows for ascertainment of relevant information from a case in a family or cohort, which is then searchable by family, OMIM number, phenotypic feature, mode of inheritance, genes screened, and so on. The database can also be used to format phenotypic data for submission to dbGaP for appropriately consented individuals. PhenoDB was built using Django, an open source Web development tool, and is freely available through the Johns Hopkins McKusick-Nathans Institute of Genetic Medicine (http://phenodb.net).</p>},
	keywords = {Databases, Factual, Genomics, Humans, Internet, Medical Informatics, Phenotype, Software},
	issn = {1098-1004},
	doi = {10.1002/humu.22283},
	author = {Hamosh, Ada and Sobreira, Nara and Hoover-Fong, Julie and Sutton, V Reid and Boehm, Corinne and Schiettecatte, Fran{\c c}ois and Valle, David}
}
