Gene/locus | Case/ctrl1 or isogenic | Cell types | Culture system2 | Synaptic phenotype3 | Phenotype rescued? | Ref | |
---|---|---|---|---|---|---|---|
Excit | Inhib4 | ||||||
22q13.3+/− | Case/ctrl | Neurons (NPC) | ASD/Ctrl co-culture w/ rt astro | ↓ sEPSC freq/ampl; ↓ exc syn#; ↓ AMPAR ampl; ↓ NMDAR ampl | No change | IGF-1 or SHANK3 transgene | [34] |
TRPC6+/− | Case/ctrl | Neurons (NPC) | Mono-culture | ↓ vGLUT1 punctae; ↓ TDL | ND | IGF-1, TRPC6 transgene, and TRPC6 agonist | [35] |
NRXN1+/− | Isogenic hESC | Excit neu (Ngn2) | Mono-culture w/ ms astro | ↓ mEPSC freq; ↓ release prob; =syn#; =TDL | NA | Not tested | [36] |
STXBP1+/− | Isogenic hESC | Excit neu (Ngn2) | Mono-culture w/ ms astro | ↓ mEPSC freq; ↓ release prob; = syn#; =TDL | NA | Not tested | [37] |
SHANK3−/− | Isogenic hESC | Excit neu (Ngn2) | Mono-culture | ↓ mEPSC freq; ↓ syn#; ↓ Ih channel function | NA | Not tested | [38] |
ASD with macrocephaly | Case/ctrl | Neurons (NPC) | Mono-culture | ↓ vGLUT1 punctae; ↓ burst freq | ND | IGF-1 (network bursts) | [39] |
Not stratified | Case/ctrl | Neurons and astro (NPC) | Reciprocal neu/astro for ASD and Ctrl | ↓ exc syn#; ↓ firing rate; (caused by ASD astro) | ND | Culture ASD neurons w/ctrl astro or block IL-6 | [40] |
10 ASD genes knocked-out with CRISPR | Isogenic iPSCs | Excit neu (Ngn2) | Mono-culture w/ms astro | ↓ sEPSC freq (5/10 genes); ↓ burst freq (4/10 genes) | NA | Not tested | [32] |
CNTN5+/− and EHMT2+/− | Case/ctrl and isogenic | Excit neu (Ngn2) | Mono-culture w/ms astro | ↑ firing rate; ↑ burst freq | NA | Not tested | [42] |
NLGN4R704C | Isogenic hESC | Neurons (Excit: AM; Inhibit: AD) | Mono-culture or co-culture on ctrl lawn w/ ms astro | ↑ syn#; ↑ mEPSC freq/ampl | No change | Not tested | [43] |
SHANK2+/− | Case/ctrl and isogenic | Neurons (NPC) | ASD/Ctrl co-culture on ctrl lawn w/ms astro | ↑ syn#; ↑ TDL; ↑ sEPSC freq/ampl | ND | Genome editing to repair SHANK2 and DHPG | [41] |
PTCHD1-AS-/y | Case/ctrl and isogenic | Neurons (NPC) | Mono-culture w/hu or ms astro | ↓ AMPAR-mEPSC freq; =exc syn#; =TDL; ↓ NMDAR ampl | ND | Not tested | [20] |
9q34+/− or EHMT1+/− | Case/ctrl and isogenic | Excit neu (Ngn2) | Mono-culture w/rt astro | ↓ burst freq; ↑ burst duration =syn#; =TLD; =AMPAR-mEPSC freq/ampl; ↑ NMDAR ampl | NA | MK-801 | [44] |