Abstract
The mammalian cerebral cortex is characterized by complex patterns of anatomical and functional areas that differ markedly between species, but the molecular basis for this functional subdivision is largely unknown. Here, we show that mutations in GPR56, which encodes an orphan G protein-coupled receptor (GPCR) with a large extracellular domain, cause a human brain cortical malformation called bilateral frontoparietal polymicrogyria (BFPP). BFPP is characterized by disorganized cortical lamination that is most severe in frontal cortex. Our data suggest that GPCR signaling plays an essential role in regional development of human cerebral cortex.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Substitution
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Animals
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Antisense Elements (Genetics)
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Biological Evolution
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Body Patterning
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Cerebral Cortex / abnormalities*
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Cerebral Cortex / embryology
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Cerebral Ventricles / cytology
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Cerebral Ventricles / embryology
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Female
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Frameshift Mutation
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Frontal Lobe / abnormalities*
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Frontal Lobe / embryology
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Gene Order
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Humans
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Ligands
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Male
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Mice
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Mutation, Missense
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Neurons / physiology
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Parietal Lobe / abnormalities
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Parietal Lobe / embryology
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Receptors, G-Protein-Coupled / chemistry
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Receptors, G-Protein-Coupled / genetics*
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Receptors, G-Protein-Coupled / metabolism
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Receptors, G-Protein-Coupled / physiology*
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Sequence Deletion
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Sequence Homology, Amino Acid
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Signal Transduction
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Stem Cells / physiology
Substances
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ADGRG1 protein, human
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Antisense Elements (Genetics)
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Ligands
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Receptors, G-Protein-Coupled