涓浠锛哄璧蜂涔浣

哄锛绉瀛ぇ

浣锛浠瀛榫锛涓界瀛㈢缁瀛绌舵锛

讹涓界瀛㈣绠虹缁淇℃腑蹇涓界瑙

1930骞翠唬缁翠绾冲1940骞翠唬宸村╋濂ュ板╃挎集硷H.Asperger锛荤涓界撼锛L. Kanner锛荤涓绾版敞颁绫诲瀛╁锛浠浠豢浣娲诲ㄨ繁涓涓涓夸汉浜ゆ锛涓瀛╁

杩浜瀛╁寰寰涓浜澶绘跨ㄤ锛涓澶璇璇妯″缂轰璇浜ゆ锛浠浠杩绉璧蜂涓涓瀛锛锛autism锛

ㄨ绂昏琚涓涓绾腑锛荤浠跨や锋缁哥跺锛朵腑灏颁汉杩锋烘璁板瓒寮轰板充规界璞°

杩骞存ワ绀句澶т瀵硅涓虫敞锛澶ч藉澶褰辫浣绾风悍虹锛璁╀汉浠杩绉绁绉剧婊′濂藉

绌剁涔瀵艰寸锛绌剁澶灏锛藉不锛

诲涓瀛娓灞锛涓村荤涓瀛绱у浣锛宸插璧峰涓灞浜涓浜浜瑙ｏ绉瀛涔ㄧ绌惰杩绋涓锛浜虹被璁稿绮剧朵哄崇郴瀵锛ㄧ绌惰杩绋涓浜虹被涔存繁诲拌璇浜韩

澶╃涓ぉ褰㈡

╃绌惰跺锛撼荤璁や负锛杩绉剧芥舵瀵瑰瀛杩锋瀵艰寸锛涔姝ｅ涓鸿凤ㄧ卞ぉ绱瀵艰寸杩涓规剧琛浜寰挎堕淬

村版绌惰锛ㄤ涓搴腑锛濡涓涓瀛ｆ锛朵瀛╁涔ｈ姒澶уぇ涓锛瀹舵腑虹ｈ锛瀹舵朵缃规ｈ姒涔澶уぇ涓杩浜璇存锋姣杈‘瀹舵浼妯″绀鸿涓浼绱瀵稿炽

浜涓浼涔璋

1998 骞村介诲瀛冲锛Lancet锛琛ㄤ涓绡ラ锛卞介灏寰凤A. Wakefield锛荤8 浣跨ㄦ绉浜楹荤广虹椋圭锛MMR锛涓寮濮虹浜讹MMR绉藉磋

姝ょ绌舵璧蜂鸿僵跺ぇ娉板挎蹇瀛╁瀹ㄨ涓㈢瀛╁绉MMR 锛ㄤ浣骞翠腑锛涓崇郴濮缁杩风

2010骞2锛缁涓ユ肩璋ュ锛杩绡绔浣瀵圭绌剁濮版ㄧ╂ч涓瀛ㄦ跺寰甯璐胯绛锛冲瀹ｅら浜杩绡寮璧峰澶т璁绔锛灏寰蜂琚卞藉浜琛绘хс

缇界剧朵蹭腑蹇2011-2013骞存杩甯浜涓绯诲绌剁锛杩澶ц妯＄版瀹楠璇8绉ㄤ垮绉涓昏瀹涓浼瀵艰磋

灏界瀹瑰凡哄锋濞ュ锛姘浼濮缁寰惧ㄦ惧锛绌剁缁瀛╁绉绉瀛绌剁杩灞锛杩浜В涔璋㈡㈣寮

棣锛蹇椤诲惧磋缃绁搁浼绱

绉瀛浠20 涓绾10 骞村濮浜瀵绘捐哄绔璧瓒ｇ浼х剧涓哄绐崇郴涔ㄥ绌朵腑寰伴拌璇

浼缁瑙硅涓猴浼х剧寰寰浠ユ惧板板绉‘寸哄锛姣濡扮剁璐寰寰辩琛绾㈣界哄绐达绉涔寰寰涓哄绐绱у稿炽

浣褰绌惰ㄦ堕句渚ｈ剁寸郴浜插浼锋杩ㄧ哥哄缁宠锛genome-wide association study锛GWAS锛规锛存灏芥惧拌ｈ涓虹‘寸哄

骞跺锛ｈ涓浼绐寰寰浜鸿寮锛浜轰村ぇ澶涓涓凤寰灏卞寸哄锛哄缁宠娉ㄥ捐寸哄杩绋涓峰ヤ板

版板ㄨ涓跺锛╁涓洪╁界版ワ缁寸哄绛ュ甫ヤ甯

浜虹被哄缁璁″

ㄤ界瀛卞涓锛浜虹被哄缁缁浜20 涓绾10 骞磋磋锛缁浜虹被哄缁30 浜夸釜纰卞鸿娴搴锛杩涓澶х椤圭绉颁浜虹被哄缁璁″锛Human Genome Project锛锛浜虹被缁浜浠ュ繁浼淇℃ㄩ㈢璁よ

ｄ锛ㄥ哄缁娴搴凡缁妫娴哄绐ュ父娈电浠濡浣瀵绘捐寸哄

哄缁娴搴杈甯哥ㄧ规哄缁ㄩㄤ俊ㄥ哄缁娴搴whole-genome sequencing锛WGS锛缂藉惧缁ㄩㄤ俊ㄥ惧娴搴whole-exome sequencing锛WES锛锛变搴纭浠锋间究瀹锛ㄥ惧娴搴涓虹瀛瀵绘鹃浼剧寸哄ㄧ涓绉瑰

ㄨ5 骞翠腑锛灏ゅ舵2014 骞达涓绯诲杩堕涓渚渚绌讹╃ㄥㄥ惧娴搴瑰ㄩ㈠句界寸哄锛惧扮稿冲哄绐绾100 澶涓

杩100澶涓哄绐浣瀵艰磋锛

绁缁瀛绌

㈢堕浼瀛娉磋В哄绐涓镐崇郴锛ｄ╃缁瀛绌讹ョ‘瀹绉哄绐绌剁瀵艰磋

绉绮剧剧锛灞浜簿绁剧寸杩簿绁瑁纰绛

绮剧剧涓浜缁琛х剧锛濡垮ㄦ捣榛锛绉拌骞寸村锛涓妫绛绛锛骞舵病剧绁缁

㈠绮剧剧ｈ锛寰寰瑕纾辨伐锋ュ澶ц杩琛浼ょ绌讹ｈ寰寰骞村跨锛浠浠寰寰句汉姝ｅ父娌锛涓楂璐ㄩ姝や藉浜绌朵磋灞缂

瀵圭缁╁瀹舵ヨ锛棣瑕瑙ｅ崇绌剁杩浜ㄨ浜轰腑绐哄瀵圭缁郴缁瑕斤

绉瀛ㄥ浼涓锛璁稿绐瑙界缂哄浜绐

绐瑙synapse锛ぇ烘锛缁涔磋琛璁烘浣锛绐瑙腑璁稿借川瑕斤绐瑙韩锋濉э涔灏辨绐瑙琛涓绯诲烘绐瑙村婵娲绘村讹杩绉濉у芥ぇ杩琛瀛璁板缁搴绛璁ょュ界绁缁╁虹

绐瑙

惧颁ｄ涓缁绐瑙瀵煎藉崇郴瀵哄瑕绌跺跺绐浜х缁

棣锛ㄨｈ涓浜哄绐奖剁界姝ｅ父斤舵锛杩ㄥ哄宸ョ规锛ㄦā寮ㄧ╋渚濡娇绫绘浜虹甸跨被锛涓ヨ稿崇哄绐锛ㄥ峰哄绐ㄧ╂ā涓瑙瀵藉虹绫讳技瀛ょ躲

绐瑙戒

ㄨｈ韬涓澶х被哄绐藉ㄤ浜ㄧ瑙腑璧风界界缂哄涓杩绫荤瑙借璐ｆ绐瑙璧锋ャ

杩涓戒腑绁缁斤neuroligin锛浣浜瑙剁锛绁缁斤neurexin锛浣浜瑙淇″剧锛瀹浠镐浣ㄤ娇绁缁村浠ヨ琛姝ｅ父淇″浼

ㄨ涓浼绛澶у芥姝わ绌惰惧板澶ㄨｈ韬绐哄锛芥互琚瑕界界哄锛褰瀹浠ㄨｈ涓绐跺锛绌惰板浠瑕с

寰烽澶ㄥneuroligin-neurexin瀹舵界缂哄ㄨｈ涓绐绔宠琛浜澶ч绌跺伐浣锛朵腑绌跺虫2007 骞村ㄨｈ涓惧扮涓涓哄绐neuoroligin3 R451C 绉绘板涓灏灏婧哄neuroligin3 涔ㄥ蜂瑰浜哄绐锛杩涓哄甫涓汉绫昏稿绐灏灞惰〃轰汉绫昏ｈ甯哥镐技琛ㄥ锛琛ㄧ洪澶绘跨琛涓哄涓挎浼村杩琛浜ゅ绛琛涓恒

椹疯寰烽澶

绌跺锛哄甫neuroligin3 R451C绐灏澶ц涓舵х瑙姝ｅ父灏澶锛芥村己

杩椤圭绌堕娆℃板ㄥ涓剧ず浜浜虹被琛ㄥ锛涔绀轰汉浠浠ョㄥ哄宸ョ规锛ㄥㄧ╂ā涓ā浜虹被锛璁ㄥ锛骞剁瑰娌荤┿

哄杩逛

ㄨ浼瀛绌朵腑锛ゅ寸瑙界缂哄绐澶锛杩骞存ヨ澶涓绫荤哄绐锛琛ㄧ涓轰娈垫蹭哄澧缂哄け锛虫疯板寮锛copy number variations锛

疯板寮涔ㄥ浜浜虹被哄缁娴搴琚变蹭烘缂哄け寰寰瀵艰村哄涓㈠け锛蹭烘澧浼瀵艰村哄杩澶锛ラや哄绐瀵艰磋借川涓уけ斤灞舵浜哄杩澶涔浼瀵艰村绁缁郴缁村

2009 骞村荤绉瀛锛ㄤ浜涓ラｈ涓涓涓插哄DNA 缁MeCP2 锛methyl CpG-binding protein 2锛缂哄虹疯扮澧

MeCP2 涓插哄DNA 缁斤锋璋哄琛ㄨ揪瑕姐1999 骞翠兼锛H. Zoghbi锛涓绉涓ラ绁缁叉х剧瑕瑕圭患寰锛Rett syndrome锛涔涓MeCP2 哄绐瀵稿筹95%圭患寰ｈ哄甫MeCP2 哄缂哄け界绐锛涓虹圭患寰ｈㄥ涓ｈ绫讳技琛ㄥ锛╂涔琚涓鸿璋辩郴纰涓绉锛autism spectrum disorders锛

杩浜璇〃哄琛ㄨ揪琛ㄨ浼瀛涓缁郴缁蹭藉稿筹濡澶辫藉寸缁叉х剧锛渚濡绛

缁板勾娣卞ョ绌讹绉瀛MeCP2 借川纭瀵圭缁绐瑙芥瑕褰卞

绌惰缁朵浜澶绉MeCP2 哄查や浆哄灏妯″锛ヨ瀵濡灏哄甫杩澶MeCP2 斤借〃虹被浼艰琛ㄥ

2006 骞翠兼绌剁灏浜MeCP2 哄杞ュ濂板哄甫浜虹被MeCP2 哄杞哄灏琛ㄧ虹姘村钩涓绀句浜ゅ琛涓虹己风绫昏琛ㄥ

杩涓妯″澶у版ㄤ绌讹浜轰滑浠ョ绌惰澶MeCP2界┒绔濡浣褰卞澶ц诧撮瑕杩涓ā藉璇浠哄绐轰钩绫诲ぇㄥ绀句氦纰跺锛澶ц绌剁浜浠涔

寸ㄧ╂ā

2007骞村规．锛P. Patterson锛绌剁ㄧ瀛姣榧娉ㄥ戒绱6锛IL-6锛规浠ヨ瀵煎浠ｅ虹剧绫昏涓簿绁瑁琛ㄥ锛杩绉规琚О涓烘婧娲伙maternal immune activation锛MIA锛

绌惰锛MIA 璇卞绫昏灏妯″涓虹浜浠ｈ阿绯荤绱涔憋瑰浠ｈ阿绱涔辩╁跺捐瑰MIA 灏妯″琛ㄥ

杩浜绌剁浠や汉锛浣跺椤昏璇帮璧峰澶绉澶凤MIA 规璇卞妯″藉瀹ㄦā浜虹被杩娣卞ョ绌躲

界跺ㄥ涓ヤ汉绫昏稿崇绐锛杩绌惰哄绐濡浣褰卞澶ц插凡缁寰澶瑕锛浣汉浠缁杩绉澶绮剧剧锛藉ㄥ娇绫绘ュ纭ā藉‘瀹灏绫昏舵汉绫荤瓒冲稿

浜虹被澶ц娌寰澶锛翠澶ц浣绉绋搴娇绫诲ㄧ╃澶ц瀹ㄦ娉姣ㄥ涓璇涓浜绁缁剧╃锛ㄤ汉绫荤ｈ韩涓涓村璇楠寰灏寰

姝わ浠ョㄨ涓涓汉绫诲敖界歌╂ユ寤鸿ㄧ╂ā杩涓

2016骞1锛涓界瀛杩ㄥ哄宸ョ规锛棣娆″颁哄甫哄MECP2杞哄达骞惰浜哄甫浜虹被哄杞哄村浠ョǔ瀹灏哄浼充涓浠ｃ

绌朵腑寰扮杞哄达浣 渚撅

杩浜哄甫浜虹被哄MECP2杞哄磋〃轰汉绫昏ｉ甯哥镐技澶绘胯涓猴涓ぞ浜よ涓洪纰锛瀵硅浜杞哄寸绌舵ㄥ灞锛杩浜妯″灏涓烘浠渚哄涓ぇ缁崇郴绗璇涓烘浠璇哄峰奖甸跨被澶ц蹭渚瑕绾跨储

浜杩浜哄甫浜虹被剧哄甸跨被妯″锛灏辨藉ㄦ存杩浜虹被ㄧ╃郴缁涓绌惰浜哄绐锋瑰甸跨被ㄧ╁ぇ锛杩寰存杩浜虹被╃绯荤

绌剁

绌惰浠璇帮浜虹被澶绀句氦琛涓烘芥杩绮惧绁缁璺ヨ锛姝ゅ绉瀛绌讹灏涓烘繁ヨ璇浜虹被绀句氦琛涓虹绁缁璺虹渚瑕绾跨储

寰浜DNA 娴搴椋杩姝ワュ浼浠ユ村娣卞ュㄩ浠ユ绀轰互娉惧扮哄绐涓蹭缁寮

ㄥ剧哄绁缁╁绌舵归绉瀛涔灏绉疮村版╀浜哄绐剧稿崇ゆ

镐俊ㄤ杩灏ワ绁缁瀛ㄨㄧ╂ā涓绌讹瀹浼甯╂浠惧板哄绐濡浣瀵艰磋虹骞查规

42ヤワ璁╂浠璧峰ゆ瀛╁锛剧ユ锛绘ワ

1. Kanner L. Irrelevant and metaphorical language in early infantile autism. Am J Psychiat, 1946, 103锛2锛: 242-246.

2. Lai M C, Lombardo M V, Baron-Cohen S. Autism. Lancet, 2014, 383锛9920锛: 896-910.

3. Weiss L A, Arking D E, Consortium J H A. A genome-wide linkage and association scan reveals novel loci for autism. Nature, 2009, 461锛7265锛: 802-808.

4. Sebat J, Lakshmi B, Malhotra D, et al. Strong association of de novo copy number mutations with autism. Science, 2007, 316锛5823锛: 445-449.

5. Tabuchi K, Blundell J, Etherton M R, et al. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science, 2007, 318锛5847锛: 71-76.

6. Jamain S, Quach H, Betancur C, et al. Mutations of the X-linked genes encoding neuroligins nlgn3 and nlgn4 are associated with autism.Nature Genetics, 2003, 34锛1锛: 27-29.

7. Ramocki M B, Peters S U, Tavyev Y J, et al. Autism and other neuropsychiatric symptoms are prevalent in individuals with Mecp2 duplication syndrome. Annals of Neurology, 2009, 66锛6锛: 771-782.

8. Amir R E, Van Den Veyver I B, Wan M, et al. Rett syndrome is caused by mutations in X -linked Mecp2, encoding methyl -Cpg binding protein 2. Nature Genetics, 1999, 23锛2锛: 185-188.

9. Samaco R C, Mandel-Brehm C, Mcgraw C M, et al. Crh and oprm1 mediate anxiety-related behavior and social approach in a mouse model of Mecp2 duplication syndrome. Nature Genetics, 2012, 44锛2锛: 206-211.

10. Hsiao E Y, Mcbride S W, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell, 2013, 155锛7锛: 1451-1463.

11. Liu H L, Chen Y C, Niu Y Y, et al. Talen-mediated gene mutagenesis in rhesus and cynomolgus monkeys. Cell Stem Cell, 2014, 14锛3锛:323-328.

锛瑙浜绉瀛蹇锛涓㈢缁渚绋匡绉瀛ぇ㈠甯剁ユ淇癸杞浇璇疯绯cas@cnic.cn锛