title: A novel GPR56 mutation causes bilateral frontoparietal polymicrogyria.
abstract: Bilateral frontoparietal polymicrogyria is an autosomal recessive inherited human brain malformation with abnormal cortical lamination. The affected cortex appears to consist of numerous small gyri, with scalloping of the cortical-white matter junction. There are associated white matter, brain stem, and cerebellar changes. Affected individuals manifest mental retardation, language impairment, motor developmental delay, and seizure disorder. GPR56 is the causative gene. Here we report a novel missense mutation of GPR56, E496K, identified in a consanguineous pedigree with bilateral frontoparietal polymicrogyria. GPR56 protein is cleaved at the G-protein-coupled receptor proteolytic site into an N- and a C-terminal fragment, named GPR56(N) and GPR56(C), respectively. E496K is located in GPR56(C). Further biochemical studies reveal that this mutation affects GPR56(C) cell surface expression similar to the effect of a previously reported mutation, R565W. These results provide further insights into how GPR56 mutation causes neurologic disease.
authors: Division of Newborn Medicine, Department of Medicine, Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Rong
authors: R
authors: Luo
authors: Hye Min
authors: HM
authors: Yang
authors: Zhaohui
authors: Z
authors: Jin
authors: Dicky J J
authors: DJ
authors: Halley
authors: Bernard S
authors: BS
authors: Chang
authors: Lesley
authors: L
authors: MacPherson
authors: Louise
authors: L
authors: Brueton
authors: Xianhua
authors: X
authors: Piao
mesh_terms: D002675:Child, Preschool; D005625:Frontal Lobe / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009421:Nervous System Malformations / Q000150:complications / Q000235:genetics / Q000473:pathology; D010296:Parietal Lobe / Q000473:pathology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: C118925:ADGRG1 protein, human; D043562:Receptors, G-Protein-Coupled