Dataset Information

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia.

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 ?-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 ?-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.

SUBMITTER: Dong W

PROVIDER: S-EPMC7554653 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia.

Dong Weilai W Jin Sheng Chih SC Allocco August A Zeng Xue X Sheth Amar H AH Panchagnula Shreyas S Castonguay Annie A Lorenzo Louis-Étienne LÉ Islam Barira B Brindle Geneviève G Bachand Karine K Hu Jamie J Sularz Agata A Gaillard Jonathan J Choi Jungmin J Dunbar Ashley A Nelson-Williams Carol C Kiziltug Emre E Furey Charuta Gavankar CG Conine Sierra S Duy Phan Q PQ Kundishora Adam J AJ Loring Erin E Li Boyang B Lu Qiongshi Q Zhou Geyu G Liu Wei W Li Xinyue X Sierant Michael C MC Mane Shrikant S Castaldi Christopher C López-Giráldez Francesc F Knight James R JR Sekula Raymond F RF Simard J Marc JM Eskandar Emad N EN Gottschalk Christopher C Moliterno Jennifer J Günel Murat M Gerrard Jason L JL Dib-Hajj Sulayman S Waxman Stephen G SG Barker Fred G FG Alper Seth L SL Chahine Mohamed M Haider Shozeb S De Koninck Yves Y Lifton Richard P RP Kahle Kristopher T KT

iScience 20200911 10

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. Mi ...[more]

PMID: 33083721

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Project description:ObjectiveTo compare complete neuroendoscopic and microscopic microvascular decompression (MVD) in primary trigeminal neuralgia (PTN) and their impacts on the microstructure of the trigeminal nerve.MethodsEighty-seven PTN patients admitted in our hospital from July 2017 to December 2019 were selected for this prospective study and divided into the endoscopic group (n=45) (complete neuroendoscopic MVD) and the microscope group (n=42) (microscopic MVD) according to the treatment method each patient underwent. All the patients underwent MRI scanning, and the fractional anisotropy (FA) scores and the apparent diffusion coefficient (ADC) values of the neurovascular compression (NVC) sites were measured. The operation times, the treatment efficacy, the microstructural changes in the trigeminal nerve, the complications, and the recurrence and mortality rates at one year after the operations were compared.ResultsThe endoscopic group observed a superior therapeutic effect compared with the microscope group one year after the surgeries (P=0.046). After the surgeries, the endoscopic group observed a greater increase in their FA values and a larger decline in their ADC values than the microscope group did (P=0.014, 0.015, 0.011, 0.002). The complication rate in the endoscopic group was 11.11%, and the complication rate in the microscopic group was 30.95% (P=0.022). One year after the surgeries, we found a lower recurrence rate in the endoscopic group (P=0.001). The perforator vessels from the offending vessel to the outlet area of the durmedulla, the distances between the front edge of the bone window and the inner surfaces of the petrous part of the temporal bone ≥ the distance between the duration ≥ the duration of conventional MVD were independent risk factors for complications after MVD in the hemifacial spasm patients (P=0.001, 0.037, 0.023, 0.005).ConclusionComplete neuroendoscopic MV yields better long-term treatment outcomes than microscopic MVD, and it is more effective at improving the microstructure of the trigeminal nerve and has fewer postoperative complications.

Dataset Information

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia.

Publications

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia.

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