Synaptic Disorders

Variability in Neural Circuit Formation

“…(Other examples of human disorders arising from mutations in guidance or connectivity genes [including CNTNAP2, L1CAM, NTNG1, and PCDH19, for example] are reviewed in Engle 2010; Blockus and Chedotal 2015;Betancur and Mitchell 2015;and Yuasa-Kawada et al 2023. ) Most of these conditions are recessive, meaning both copies of the gene must be mutated to cause the phenotype (as is commonly observed for axon guidance genes in model organisms).…”

“…Risk genes are generally enriched for genes expressed in fetal brain and involved more broadly in neurodevelopmental processes. These include processes "upstream" of circuit specification, like regulation of gene expression and chromatin function, as well as "downstream" processes like synaptic plasticity or function, which may impact on activity-dependent refinement of neural circuits (e.g., NMDA-receptor genes like GRIN2A or synaptic protein genes like SHANK3 or SYN-GAP1; Betancur and Mitchell 2015). However, there are also many genes implicated in these illnesses where neither a direct nor indirect link to the processes of circuit formation or refinement is apparent.…”

An Investigation of SDF1/CXCR4 Gene Polymorphisms in Autism Spectrum Disorder: A Family-Based Study

“…Different genetic disorders are known to cause the characteristic ASD phenotype through similar mechanisms [ 13 ]. IL1RAPL1 gene mutation encoding a protein affecting the interleukin-1 receptor that regulates cytokine activity has been associated with ASD [ 14 ]. A decreased 22q11.2 gene level disrupts the migration and positioning of neurons in the brain via CXCR4 [ 15 ].…”