Sökning: onr:"swepub:oai:DiVA.org:uu-527816" > Identification of u...
Fältnamn | Indikatorer | Metadata |
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000 | 04203naa a2200493 4500 | |
001 | oai:DiVA.org:uu-527816 | |
003 | SwePub | |
008 | 240509s2022 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5278162 URI |
024 | 7 | a https://doi.org/10.1038/s41598-022-15279-32 DOI |
040 | a (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Trifiletti, Rosario4 aut |
245 | 1 0 | a Identification of ultra-rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing |
264 | c 2022-06-30 | |
264 | 1 | b Springer Nature,c 2022 |
338 | a electronic2 rdacarrier | |
520 | a Abrupt onset of severe neuropsychiatric symptoms including obsessive–compulsive disorder, tics, anxiety, mood swings, irritability, and restricted eating is described in children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). Symptom onset is often temporally associated with infections, suggesting an underlying autoimmune/autoinflammatory etiology, although direct evidence is often lacking. The pathological mechanisms are likely heterogeneous, but we hypothesize convergence on one or more biological pathways. Consequently, we conducted whole exome sequencing (WES) on a U.S. cohort of 386 cases, and whole genome sequencing (WGS) on ten cases from the European Union who were selected because of severe PANS. We focused on identifying potentially deleterious genetic variants that were de novo or ultra-rare (MAF) < 0.001. Candidate mutations were found in 11 genes (PPM1D, SGCE, PLCG2, NLRC4, CACNA1B, SHANK3, CHK2, GRIN2A, RAG1, GABRG2, and SYNGAP1) in 21 cases, which included two or more unrelated subjects with ultra-rare variants in four genes. These genes converge into two broad functional categories. One regulates peripheral immune responses and microglia (PPM1D, CHK2, NLRC4, RAG1, PLCG2). The other is expressed primarily at neuronal synapses (SHANK3, SYNGAP1, GRIN2A, GABRG2, CACNA1B, SGCE). Mutations in these neuronal genes are also described in autism spectrum disorder and myoclonus-dystonia. In fact, 12/21 cases developed PANS superimposed on a preexisting neurodevelopmental disorder. Genes in both categories are also highly expressed in the enteric nervous system and the choroid plexus. Thus, genetic variation in PANS candidate genes may function by disrupting peripheral and central immune functions, neurotransmission, and/or the blood-CSF/brain barriers following stressors such as infection. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Psykiatri0 (SwePub)302152 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Psychiatry0 (SwePub)302152 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
700 | 1 | a Lachman, Herbert M.4 aut |
700 | 1 | a Manusama, Olivia4 aut |
700 | 1 | a Zheng, Deyou4 aut |
700 | 1 | a Spalice, Alberto4 aut |
700 | 1 | a Chiurazzi, Pietro4 aut |
700 | 1 | a Schornagel, Allan4 aut |
700 | 1 | a Serban, Andreea M.4 aut |
700 | 1 | a van Wijck, Rogier4 aut |
700 | 1 | a Cunningham, Janet L.u Uppsala universitet,Psykiatri4 aut0 (Swepub:uu)janecunn |
700 | 1 | a Swagemakers, Sigrid4 aut |
700 | 1 | a van der Spek, Peter J.4 aut |
710 | 2 | a Uppsala universitetb Psykiatri4 org |
773 | 0 | t Scientific Reportsd : Springer Natureg 12:1q 12:1x 2045-2322 |
856 | 4 | u https://doi.org/10.1038/s41598-022-15279-3y Fulltext |
856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1856998/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-527816 |
856 | 4 8 | u https://doi.org/10.1038/s41598-022-15279-3 |
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