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- W4288736489 abstract "ADGRL1 (latrophilin 1), a well-characterized adhesion G protein-coupled receptor, has been implicated in synaptic development, maturation, and activity. However, the role of ADGRL1 in human disease has been elusive. Here, we describe ten individuals with variable neurodevelopmental features including developmental delay, intellectual disability, attention deficit hyperactivity and autism spectrum disorders, and epilepsy, all heterozygous for variants in ADGRL1. In vitro, human ADGRL1 variants expressed in neuroblastoma cells showed faulty ligand-induced regulation of intracellular Ca2+ influx, consistent with haploinsufficiency. In vivo, Adgrl1 was knocked out in mice and studied on two genetic backgrounds. On a non-permissive background, mice carrying a heterozygous Adgrl1 null allele exhibited neurological and developmental abnormalities, while homozygous mice were non-viable. On a permissive background, knockout animals were also born at sub-Mendelian ratios, but many Adgrl1 null mice survived gestation and reached adulthood. Adgrl1-/- mice demonstrated stereotypic behaviors, sexual dysfunction, bimodal extremes of locomotion, augmented startle reflex, and attenuated pre-pulse inhibition, which responded to risperidone. Ex vivo synaptic preparations displayed increased spontaneous exocytosis of dopamine, acetylcholine, and glutamate, but Adgrl1-/- neurons formed synapses in vitro poorly. Overall, our findings demonstrate that ADGRL1 haploinsufficiency leads to consistent developmental, neurological, and behavioral abnormalities in mice and humans." @default.
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- W4288736489 date "2022-08-01" @default.
- W4288736489 modified "2023-09-30" @default.
- W4288736489 title "ADGRL1 haploinsufficiency causes a variable spectrum of neurodevelopmental disorders in humans and alters synaptic activity and behavior in a mouse model" @default.
- W4288736489 cites W1574280714 @default.
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- W4288736489 cites W1966354110 @default.
- W4288736489 cites W1973529660 @default.
- W4288736489 cites W1974313494 @default.
- W4288736489 cites W1979208523 @default.
- W4288736489 cites W1980112246 @default.
- W4288736489 cites W1983555571 @default.
- W4288736489 cites W1984305433 @default.
- W4288736489 cites W1984875318 @default.
- W4288736489 cites W1986941314 @default.
- W4288736489 cites W1987707300 @default.
- W4288736489 cites W1988450443 @default.
- W4288736489 cites W1990936275 @default.
- W4288736489 cites W1993149363 @default.
- W4288736489 cites W1994852479 @default.
- W4288736489 cites W1995852110 @default.
- W4288736489 cites W2004066481 @default.
- W4288736489 cites W2010726206 @default.
- W4288736489 cites W2020858284 @default.
- W4288736489 cites W2025095843 @default.
- W4288736489 cites W2036077355 @default.
- W4288736489 cites W2039055179 @default.
- W4288736489 cites W2040479508 @default.
- W4288736489 cites W2049398301 @default.
- W4288736489 cites W2051561558 @default.
- W4288736489 cites W2052123563 @default.
- W4288736489 cites W2062472783 @default.
- W4288736489 cites W2064181852 @default.
- W4288736489 cites W2071797996 @default.
- W4288736489 cites W2074363868 @default.
- W4288736489 cites W2075665232 @default.
- W4288736489 cites W2083275500 @default.
- W4288736489 cites W2084395458 @default.
- W4288736489 cites W2085548674 @default.
- W4288736489 cites W2087924977 @default.
- W4288736489 cites W2089079245 @default.
- W4288736489 cites W2095314858 @default.
- W4288736489 cites W2096349664 @default.
- W4288736489 cites W2098523005 @default.
- W4288736489 cites W2108994842 @default.
- W4288736489 cites W2111689719 @default.
- W4288736489 cites W2115716038 @default.
- W4288736489 cites W2130955385 @default.
- W4288736489 cites W2138630674 @default.
- W4288736489 cites W2141884799 @default.
- W4288736489 cites W2148512452 @default.
- W4288736489 cites W2149161655 @default.
- W4288736489 cites W2150633163 @default.
- W4288736489 cites W2153752758 @default.
- W4288736489 cites W2155958967 @default.