The Potential Effect of Na(v)1.8 in Autism Spectrum Disorder: Evidence From a Congenital Case With Compound Heterozygous SCN10A Mutations

作者全名："Heinrichs, Bjoern; Liu, Baowen; Zhang, Jin; Meents, Jannis E.; Le, Kim; Erickson, Andelain; Hautvast, Petra; Zhu, Xiwen; Li, Ningbo; Liu, Yi; Spehr, Marc; Habel, Ute; Rothermel, Markus; Namer, Barbara; Zhang, Xianwei; Lampert, Angelika; Duan, Guangyou"

作者地址："[Heinrichs, Bjoern; Meents, Jannis E.; Erickson, Andelain; Hautvast, Petra; Lampert, Angelika] Uniklin RWTH Aachen Univ, Inst Physiol, Aachen, Germany; [Liu, Baowen; Zhu, Xiwen; Duan, Guangyou] Chongqing Med Univ, Affiliated Hosp 2, Dept Anesthesiol, Chongqing, Peoples R China; [Liu, Baowen; Zhang, Jin; Li, Ningbo; Liu, Yi; Zhang, Xianwei] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Anesthesiol, Wuhan, Peoples R China; [Le, Kim] Rhein Westfal TH Aachen, Inst Biol 2, Dept Chemosensat, AG Neuromodulat, Aachen, Germany; [Spehr, Marc] Rhein Westfal TH Aachen, Inst Biol 2, Dept Chemosensat, Aachen, Germany; [Habel, Ute] Uniklin RWTH Aachen Univ, Dept Psychiat Psychotherapy & Psychosomat, Aachen, Germany; [Habel, Ute] Forschungszentrum Julich, JARA BRAIN Inst Brain Struct Funct Relationships, Aachen, Germany; [Habel, Ute] Rhein Westfal TH Aachen, Aachen, Germany; [Rothermel, Markus] Univ Vet Med, Inst Physiol & Cell Biol, Hannover, Germany; [Namer, Barbara] Rhein Westfal TH Aachen, Fac Med, Res Grp Neurosci, Interdisciplinary Ctr Clin Res IZKF, Aachen, Germany"

通信作者："Lampert, A (corresponding author), Uniklin RWTH Aachen Univ, Inst Physiol, Aachen, Germany.; Duan, GY (corresponding author), Chongqing Med Univ, Affiliated Hosp 2, Dept Anesthesiol, Chongqing, Peoples R China."

来源：FRONTIERS IN MOLECULAR NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000683313300001

JCR分区：Q2

影响因子：4.8

年份：2021

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：SCN10A/Nav1.8; autism spectrum disorder; p.I1511M; p.R512~; genetic; mutation

摘要："Apart from the most prominent symptoms in Autism spectrum disorder (ASD), namely deficits in social interaction, communication and repetitive behavior, patients often show abnormal sensory reactivity to environmental stimuli. Especially potentially painful stimuli are reported to be experienced in a different way compared to healthy persons. In our present study, we identified an ASD patient carrying compound heterozygous mutations in the voltage-gated sodium channel (VGSC) Na(v)1.8, which is preferentially expressed in sensory neurons. We expressed both mutations, p.I1511M and p.R512*, in a heterologous expression system and investigated their biophysical properties using patch-clamp recordings. The results of these experiments reveal that the p.R512* mutation renders the channel non-functional, while the p.I1511M mutation showed only minor effects on the channel's function. Behavioral experiments in a Na(v)1.8 loss-of-function mouse model additionally revealed that Na(v)1.8 may play a role in autism-like symptomatology. Our results present Na(v)1.8 as a protein potentially involved in ASD pathophysiology and may therefore offer new insights into the genetic basis of this disease."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81701096]; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)German Research Foundation (DFG) [LA2740/3-1, 363055819/GRK2415, 368482240/GRK24 16, RO4046/2-1, RO4046/2-2]; Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University [IZKF TN1-1/IA 532001, TN1-7/IA 532007, TN1-8/IA 532008]; Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University"

基金资助正文："This work was supported by National Natural Science Foundation of China (No. 81701096), by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, LA2740/3-1; 363055819/GRK2415 to AL, and 368482240/GRK24 16 to MS, MR, and AL, RO4046/2-1 and/2-2, Emmy Noether Program to MR) and by a grant from the Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University (IZKF TN1-1/IA 532001, TN1-7/IA 532007 and TN1-8/IA 532008). BN is supported by a grant from the Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University."