ADGRL1 haploinsufficiency causes a variable spectrum of neurodevelopmental disorders in humans and alters synaptic activity and behavior in a mouse model
ADGRL1 (Latrophilin 1), a receptor for α-latrotoxin from the black widow spider, can modulate neurotransmitter release in neurons, but so far no data directly linked it to a heritable condition. A team of scientists from the Laboratory of microfluidic technologies for biomedicine IBCh RAS in collaboration with colleagues from other Russian and foreign institutions showed that individuals heterozygous for different pathogenic variants of ADGRL1 display various neuro-psychiatric features, including developmental delay, intellectual disability, attention deficit/hyperactivity, autism spectrum disorders and epilepsy. In vitro, these pathogenic variants encode receptors with perturbed functions. Adgrl1 knockout mice have altered neurotransmitter release and deficient synapse formation in culture, and show neurological and developmental abnormalities similar to human conditions. The data demonstrate that ADGRL1 haploinsufficiency causes developmental, neurological and behavioral abnormalities in mice and humans, clearly linking ADGRL1 receptor to important CNS functions. The results are publushed in the American Journal of Human Genetics.
august 9, 2022