Segnalo l’articolo Rare structural variation of synapse and neurotransmission genes in autism X Gai1, H M Xie1, J C Perin1, N Takahashi2, K Murphy1, A S Wenocur1, M D'arcy1, R J O'Hara1, E Goldmuntz3,6, D E Grice4, T H Shaikh5, H Hakonarson6,7,8, J D Buxbaum2, J Elia9,10 and P S White1,6,11 Molecular Psychiatryadvance online publication 1 March 2011; doi: 10.1038/mp.2011.10 L’articolo puo’ essere letto integralmente al link http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201110a.html Gli autori hanno studiato le CNVs (genome copy-number variations) in campioni numericamente consistenti di persone con autismo e in campioni di controllo. Numericamente le CNV sono frequenti sia nei probandi che nei controlli. Gli autori si sono quindi focalizzati sulle CNV presenti solo nelle persone con autismo per risalire dai geni alla funzione da essi codificata. Questo tipo di ricerca ha condotto alla funzione sinaptica e alla neurotrasmissione. Copio alcuni stralci “In this study we show that biological processes associated with synapse function and neurotransmission are significantly enriched, with replication, in ASD subjects versus controls” Gli autori hanno poi studiato dei modelli animali portatori di anomalie dei geni contenuti nelle CNV trovando conferma di una correlazione tra genotipo e fenotipo similautistico(abnormal (±CNS) synaptic transmission, abnormal motor capabilities/coordination/movement, abnormal motor coordination/balance, reduced NMDA-mediated synaptic currents, abnormal impulse conducting system conduction, decreased startle reflex, abnormal miniature excitatory postsynaptic currentsand abnormal spatial learning) “Analysis of phenotypes observed for mouse models of copy-variant genes established significant and replicated enrichment of observable phenotypes consistent with ASD behaviors” Gli autori pertanto concludono “These results implicate several new variants that involve synaptic function and glutamatergic signaling processes as important contributors of ASD pathophysiology” Entrando più nel particolare copio altri stralci “A total of 395 inherited CNVs (135 duplications, 256 heterozygous deletions and 4 hemizygous deletions of the X chromosome) were identified in 286 autism subjects that were not present in healthy controls Many of these processes were associated with synaptic function and neurotransmission, including cell–cell signaling (P=1.97 × 10−7), transmission of nerve impulse (P=7.06 × 10−5), synaptic transmission (P=8.05 × 10−5), neuron adhesion (P=2.06 × 10−3), central nervous system development (P=4.30 × 10−3), regulation of neurotransmitter levels (P=4.88 × 10−3), neurotransmitter secretion (P=1.30 × 10−2) and neurotransmitter transport (P=2.95 × 10−2). Autism CNV genes frequently associated with terms related to synapse function and neurotransmission included previous candidates CNTN4, NRXN1 and PARK2, as well as genes CNTN6, CTNND2, GRIN2A, NCAM2, GRM7, GRM8 and RCAN1. Le conclusioni degli autori sono le seguenti “our results do consistently and independently implicate possible pathways, functions and gene sets that can be readily investigated by follow-up genomic and experimental investigation. Our current results extend these findings and, more importantly, for the first time provide statistical evidence that synaptic function and glutamate-mediated neurotransmission are contributing factors in autism etiology” Lo spostamento dai geni alle sinapsi e alla neurotrasmissione dovrebbe stimolare la ricerca di target per nuovi farmaci. Sappiamo che dall’ipotesi alla commercializzazione di un farmaco la strada è lunga, ma, come dice Gianni Rodari “Chi non parte in verità in nessun posto arriverà”