| Title: | Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia |
| Journal: | iScience |
| Published: | 11 Sep 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33083721/ |
| DOI: | https://doi.org/10.1016/j.isci.2020.101552 |
| URL: | http://www.cell.com/article/S2589004220307446/pdf |
Publication 9229
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Abstract
Trigeminal 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.</p>
49 Authors
- Weilai Dong
- Sheng Chih Jin
- August Allocco
- Xue Zeng
- Amar H. Sheth
- Shreyas Panchagnula
- Annie Castonguay
- Louis-Étienne Lorenzo
- Barira Islam
- Geneviève Brindle
- Karine Bachand
- Jamie Hu
- Agata Sularz
- Jonathan Gaillard
- Jungmin Choi
- Ashley Dunbar
- Carol Nelson-Williams
- Emre Kiziltug
- Charuta Gavankar Furey
- Sierra Conine
- Phan Q. Duy
- Adam J. Kundishora
- Erin Loring
- Boyang Li
- Qiongshi Lu
- Geyu Zhou
- Wei Liu
- Xinyue Li
- Michael C. Sierant
- Shrikant Mane
- Christopher Castaldi
- Francesc López-Giráldez
- James R. Knight
- Raymond F. Sekula
- J. Marc Simard
- Emad N. Eskandar
- Christopher Gottschalk
- Jennifer Moliterno
- Murat Günel
- Jason L. Gerrard
- Sulayman Dib-Hajj
- Stephen G. Waxman
- Fred G. Barker
- Seth L. Alper
- Mohamed Chahine
- Shozeb Haider
- Yves De Koninck
- Richard P. Lifton
- Kristopher T. Kahle
1 Application
| Application ID | Title |
|---|---|
| 29900 | Defining physical activity phenotypes based on objective measures and dissecting the genetic and phenotypic relationships of physical activity with diseases and health outcomes |
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