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Sökning: WFRF:(Serban Andreea M.) > (2022) > Identification of u...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004203naa a2200493 4500
001oai:DiVA.org:uu-527816
003SwePub
008240509s2022 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5278162 URI
0247 a https://doi.org/10.1038/s41598-022-15279-32 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Trifiletti, Rosario4 aut
2451 0a 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 1b 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 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Psykiatri0 (SwePub)302152 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Psychiatry0 (SwePub)302152 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng
7001 a Lachman, Herbert M.4 aut
7001 a Manusama, Olivia4 aut
7001 a Zheng, Deyou4 aut
7001 a Spalice, Alberto4 aut
7001 a Chiurazzi, Pietro4 aut
7001 a Schornagel, Allan4 aut
7001 a Serban, Andreea M.4 aut
7001 a van Wijck, Rogier4 aut
7001 a Cunningham, Janet L.u Uppsala universitet,Psykiatri4 aut0 (Swepub:uu)janecunn
7001 a Swagemakers, Sigrid4 aut
7001 a van der Spek, Peter J.4 aut
7102 a Uppsala universitetb Psykiatri4 org
7730 t Scientific Reportsd : Springer Natureg 12:1q 12:1x 2045-2322
8564 u https://doi.org/10.1038/s41598-022-15279-3y Fulltext
8564 u https://uu.diva-portal.org/smash/get/diva2:1856998/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-527816
8564 8u https://doi.org/10.1038/s41598-022-15279-3

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