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dc.contributor.authorDong, Weilai
dc.contributor.authorJin, Sheng Chih
dc.contributor.authorAllocco, August
dc.contributor.authorZeng, Xue
dc.contributor.authorSheth, Amar H.
dc.contributor.authorPanchagnula, Shreyas
dc.contributor.authorCastonguay, Annie
dc.contributor.authorLorenzo, Louis Étienne
dc.contributor.authorIslam, Barira
dc.contributor.authorBrindle, Geneviève
dc.contributor.authorBachand, Karine
dc.contributor.authorHu, Jamie
dc.contributor.authorSularz, Agata
dc.contributor.authorGaillard, Jonathan
dc.contributor.authorChoi, Jungmin
dc.contributor.authorDunbar, Ashley
dc.contributor.authorNelson-Williams, Carol
dc.contributor.authorKiziltug, Emre
dc.contributor.authorFurey, Charuta Gavankar
dc.contributor.authorConine, Sierra
dc.contributor.authorDuy, Phan Q.
dc.contributor.authorKundishora, Adam J.
dc.contributor.authorLoring, Erin
dc.contributor.authorLi, Boyang
dc.contributor.authorLu, Qiongshi
dc.contributor.authorZhou, Geyu
dc.contributor.authorLiu, Wei
dc.contributor.authorLi, Xinyue
dc.contributor.authorSierant, Michael C.
dc.contributor.authorMane, Shrikant
dc.contributor.authorCastaldi, Christopher
dc.contributor.authorLópez-Giráldez, Francesc
dc.contributor.authorKnight, James R.
dc.contributor.authorSekula, Raymond F.
dc.contributor.authorSimard, J. Marc
dc.contributor.authorEskandar, Emad N.
dc.contributor.authorGottschalk, Christopher
dc.contributor.authorMoliterno, Jennifer
dc.contributor.authorGünel, Murat
dc.contributor.authorGerrard, Jason L.
dc.contributor.authorDib-Hajj, Sulayman
dc.contributor.authorWaxman, Stephen G.
dc.contributor.authorBarker, Fred G.
dc.contributor.authorAlper, Seth L.
dc.contributor.authorChahine, Mohamed
dc.contributor.authorHaider, Shozeb
dc.contributor.authorDe Koninck, Yves
dc.contributor.authorLifton, Richard P.
dc.contributor.authorKahle, Kristopher T.
dc.date.accessioned2020-10-16T17:07:39Z
dc.date.available2020-10-16T17:07:39Z
dc.date.issued2020-10-23
dc.identifier.urihttp://hdl.handle.net/10713/13876
dc.description.abstractTrigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated de novo mutation (p.Cys188Trp) in the GABAA receptor Cl− channel γ-1 subunit (GABRG1) exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na+ and Ca+ channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca2+ channel Cav3.2 (CACNA1H). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis.en_US
dc.description.sponsorshipAmerican Heart Associationen_US
dc.description.urihttps://doi.org/10.1016/j.isci.2020.101552en_US
dc.language.isoenen_US
dc.publisherElsevier Ltd.en_US
dc.relation.ispartofiScienceen_US
dc.subjectGenomicsen_US
dc.subjectNeuroscienceen_US
dc.subjectStructural Biologyen_US
dc.titleExome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgiaen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.isci.2020.101552
dc.source.volume23
dc.source.issue10


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