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1、项目名称：遗传性神经肌肉病的新致病基因鉴定和发病机制研究候选人：王朝霞、邓健文、袁云、于佳希、洪道俊、孟令超、谢志颖、朱笠、张巍、俞萌、吕鹤、郑艺明、赵亚雯、刚蔷、刘江红候选单位：北京大学第一医院、中国科学院生物物理研究所、南昌大学第一附属医院提名意见：神经肌肉病是一类高致残疾病，危害性大，大多缺乏精准诊断和有效治疗方法。该团队围绕这类疾病的遗传基因和发病机制开展深入研究。首次发现眼咽远端肌病(OPDM)的三个新致病基因，解释了70%患者的遗传病因，解决了该病困扰临床数十年来的基因诊断问题，立足北京，服务全国多家医院的基因检测，积极转化基因检测试剂盒的临床应用。在此基础上，基于致病基因的发病机
2、制研究，率先发现FUS、TDP-43蛋白介导线粒体损伤的分子机制，提出线粒体作为重要干预靶点，为疾病治疗提供理论基础。以上发现提高了我国在遗传性神经肌肉病诊断和治疗研究领域的国际影响力，技术指标达到国内领先和国际先进水平，研究成果具有重要的应用价值和良好的社会效益。同意推荐北京市科学技术奖。主要支撑材料目录：1. DengJ,YuJ,LiP,LuanX,CaoL,ZhaoJ,YuM,ZhangW,LvH,XieZ,MengL,ZhengY,ZhaoY,GangQ,WangQ,LiuJ,ZhuM,GuoX,SuY,LiangY,LiangF,HayashiT,MaedaMH,SatoT,UraS
3、,OyaY,OgasawaraM,IidaA,NishinoI,ZhouC,YanC,YuanY,HongD,WangZ.ExpansionofGGCRepeatinGIPClIsAssociatedwithOculopharyngodistalMyopathy.AmJHumGenet.2020Jun4;106(6):793-804.2. YuJ,DengJ,GuoX,ShanJ,LuanX,CaoL,ZhaoJ,YuM,ZhangW,LvH,XieZ,MengL,ZhengY,ZhaoY,GangQ,WangQ,LiuJ,ZhuM,ZhouB,LiP,LiuY,WangY,YanC,Hong
4、D,YuanY,WangZ.TheGGCrepeatexpansioninN0TCH2NLCisassociatedwithOculopharyngodistalmyopathytype3.Brain.2021Jul28;144(6):1819-1832.3. YuJ,ShanJ,YuM,DiL,XieZ,ZhangW,LvH,MengL,ZhengY,ZhaoY,GangQ,GuoX,WangY,XiJ,ZhuW,DaY,HongD,YuanY,YanC,WangZ,DengJ.TheCGGrepeatexpansioninRILPLlisassociatedwithOculopharyng
5、odistalmyopathytype4.AmJHumGenet.2022Mar3;109:533-541.4. DengJ,WangP,ChenX,ChengH,LiuJ,FushimiK,ZhuL,WuJY.FUSinteractswithATPsynthasebetasubunitandinducesmitochondrialunfoldedproteinresponseincellularandanimalmodels.ProcNatlAcadSciUSA.2018Oct9;115(41):E9678-E9686.5. WangP,DengJ,DongJ,LiuJ,BigioEH,Me
6、sulamM,WangT,SunL,WangL,LeeAY,McGeeWA,ChenX,FushimiK,ZhuL,WuJY.TDP-43inducesmitochondrialdamageandactivatesthemitochondrialunfoldedproteinresponse.PLoSGenet.2019May17;15(5):e.6. DengJ,YangM,ChenY,ChenX,LiuJ,SunS,ChengH,LiY,BigioEH,MesulamM,XuQ,DuS,FushimiK,ZhuL,WuJY.FUSInteractswithHSP60toPromoteMit
7、ochondrialDamage.PLoSGenet.2015Sep3;1l(9):e.7. ChenY,DengJ,WangP,YangM,ChenX,ZhuL,LiuJ,LuB,ShenY,FushimiK,XuQ,WuJY.PINKlandParkinaregeneticmodifiersforFUS-inducedneurodegeneration.HumMolGenet.2016Dec1;25(23):5059-5068.8. YuJ,LuanXH,YuM,ZhangW,LvH,CaoL,MengL,ZhuM,ZhouB,WuXR,LiP,GangQ,LiuJ,ShiX,LiangW
8、,JiaZ,YaoS,YuanY,DengJ,HongD,WangZ.GGCrepeatexpansionsinN0TCH2NLCcausingaphenotypeofdistalmotorneuropathyandmyopathy.AnnClinTranslNeurol.2021Jun;8(6):1330-1342.9. DengJ,ZhouB,YuJ,HanX,FuJ,LiX,XieX,ZhuM,ZhengY,GuoX,LiP,WangQ,LiuJ,ZhangW,YuanY,YaoS,WangZ,HongD.GeneticoriginofsporadiccasesandRNAtoxicit
9、yinneuronalintranuclearinclusiondisease.JMedGenet.2022May;59(5):462-469.10. DengJ,GuM,MiaoY,YaoS,ZhuM,FangP,YuX,LiP,SuY,HuangJ,ZhangJ,YuJ,LiF,BaiJ,SunW,HuangY,YuanY,HongD,WangZ.Long-readsequencingidentifiedrepeatexpansionsinthe5UTRoftheN0TCH2NLCgenefromChinesepatientswithneuronalintranuclearinclusio
10、ndisease.JMedGenet.2019Nov;56(11):758-764.11. DengJ,WuW,XieZ,GangQ,YuM,LiuJ,WangQ,LvH,ZhangW,HuangY,WangT,YuanY,HongD,WangZ.NovelandRecurrentMutationsinaCohortofChinesePatientsWithYoung-OnsetAmyotrophicLateralSclerosis.FrontNeurosci.2019Dec6;13:1289.12. XieZ,SunC,LiuY,YuM,ZhengY,MengL,WangG,Cornejo-
11、SanchezDM,BharadwajT,YanJ,ZhangL,Pineda-TnyilloN,ZhangW,LealSM,SchrauwenI,WangZ,YuanY.Practicalapproachtothegeneticdiagnosisofunsolveddystrophinopathies:astepwisestrategyinthegenomicera.JMedGenet.2021Nov;58(l1):743-751.13. XieZ,SunC,ZhangS,LiuY,YuM,ZhengY,MengL,AcharyaA,Cornejo-SanchezDM,WangG,Zhang
12、W,SchrauwenI,LealSM,WangZ,YuanY.Long-readwhole-genomesequencingforthegeneticdiagnosisofdystrophinopathies.AnnClinTranslNeurol.2020Oct;7(10):2041-2046.14. XieZ,XieZ,YuM,ZhengY,SunC,LiuY,LingC,ZhuY,ZhangW,XiaoJ,WangZ,YuanY.Valueofmusclemagneticresonanceimaginginthedifferentialdiagnosisofmusculardystro
13、phiesrelatedtothedystrophin-glycoproteincomplex.OrphanetJRareDis.2019Nov12;14(l):250.15. YUM,ZhaoX,WuW,WangQ,LiuJ,ZhangW,YuanY,HongD,WangZ,DengJ.WidespreadMislocalizationofFUSIsAssociatedWithMitochondrialAbnormalitiesinSkeletalMuscleinAmyotrophicLateralSclerosisWithFUSMutations.JNeuropatholExpNeurol
14、.2022Feb24;81(3):172-181.16. WangH,YuJ,YuM,DengJ,ZhangW,LvH,LiuJ,ShiX,LiangW,JiaZ,HongD,MengL,WangZ,YuanY.GGCRepeatExpansionintheN0TCH2NLCGeneIsAssociatedWithaPhenotypeofPredominantMotor-SensoryandAutonomicNeuropathy.FrontGenet.2021Jul7;12:694790.17. ZhaoY,LiY,BianY,YaoS,LiuP,YuM,ZhangW,WangZ,YuanY.
15、CongenitalmyasthenicsyndromeinChina:geneticandmyopathologicalcharacterization.AnnClinTranslNeurol.2021Apr;8(4):898-907.18. DuK,LiF,WangH,MiaoY,LvH,ZhangW,WangZ,YuanY,MengL.HereditarytransthyretinamyloidosisinmainlandChina:aunicentricretrospectivestudy.AnnClinTranslNeurol.2021Apr;8(4):831-841.19. Zha
16、ngW,WenB,LuJ,ZhaoY,HongD,ZhaoZ,ZhangC,LuoY,QiX,ZhangY,SongX,ZhaoY,ZhaoC,HuJ,YangH,WangZ,YanC,YuanY.NeutrallipidstoragediseasewithmyopathyinChina:alargemulticentriccohortstudy.OrphanetJRareDis.2019Oct26;14(1):234.20. YuM,ZhuY,XieZ,ZhengY,XiaoJ,ZhangW,NishinoI,YuanY,WangZ.NovelTTNmutationsandmuscleima
17、gingcharacteristicsincongenitaltitinopathy.AnnClinTranslNeurol.2019Jul;6(7):1311-1318.21. HouY,XieZ,ZhaoX,YuanY,DouP,WangZ.Appendicularskeletalmusclemass:AmoresensitivebiomarkerofdiseaseseveritythanBMIinadultswithmitochondrialdiseases.PLoSOne.2019Jul25;14(7):e.22. HuZ,ZhuY,LiuX,ZhangW,LiuJ,WuS,XiaoJ
18、,YuanY,WangZ.FHL!-relatedclinical,muscleMRIandgeneticfeaturesinsixChinesepatientswithreducingbodymyopathy.JHumGenet.2019Sep;64(9):919-926.23. YinL,XieZY,XuHY,ZhengSS,WangZX,XiaoJX,YuanY.T2MappingandFatQuantificationofThighMusclesinChildrenwithDuchenneMuscularDystrophy.CurrMedSci.2019Feb;39(l):138-14
19、5.24. XieZ,HouY,YuM,LiuY,FanY,ZhangW,WangZ,XiongH,YuanY.ClinicalandgeneticspectrumofSarcoglycanopathiesinalargecohortofChinesepatients.OrphanetJRareDis.2019Feb14;14(1):43.25. XieZ,XiaoJ,ZhengY,WangZ,YuanY.MagneticResonanceImagingFindingsintheMuscleTissueofPatientswithLimbGirdleMuscularDystrophyType2
20、1HarboringtheFounderMutationc.545AGintheFKRPGene.BiomedResInt.2018May29;2018:.26. MengL,FuJ,LvH,ZhangW,WangZ,YuanY.NovelmutationsinHINTlgenecauseautosomalrecessiveaxonalneuropathywithneuromyotoniaintwocasesofsensorimotorneuropathyandonecaseofmotorneuropathy.NeuromusculDisord.2018Aug;28:646-651.27. 1
21、.uY,WuR,MengL,LvH,LiuJ,ZuoY,ZhangW,YuanY,WangZ.HADHBmutationscauseinfantile-onsetaxonalCharcot-Marie-Toothdisease:Areportoftwocases.ClinNeuropathol.2018Sep/Oct;37(5):232-238.28. 1.inHT,LiuX,ZhangW,LiuJ,ZuoYH,XiaoJX,ZhuY,YuanY,WangZX.MuscleMagneticResonanceImaginginPatientswithVariousClinicalSubtypes
22、ofLMNA-RelatedMuscularDystrophy.ChinMedJ(Engl).2018Jun20;131(12):1472-1479.29. ZhangZ,ZhaoD,ZhangX,XiongH,BaoX,YuanY,WangZ.SurvivalanalysisofacohortofChinesepatientswithmitochondrialencephalomyopathywithlacticacidosisandstroke-likeepisodes(MELAS)basedonclinicalfeatures.JNeurolSci.2018Feb15;385:151-I55.30. ZhaoYW,LiuXJ,ZhangW,WangZX,YuanY.MuscleMagneticResonanceImagingfortheDifferentiationofMultipleAcyl-CoADehydrogenaseDeficiencyandImmune-mediatedNecrotizingMyopathy.ChinMedJ(Engl).2018Jan20;131(2):144-150.
