title: Bilateral frontoparietal polymicrogyria, Lennox-Gastaut syndrome, and GPR56 gene mutations.
abstract: OBJECTIVE
  Bilateral frontoparietal polymicrogyria (BFPP) has been reported in sporadic patients and in recessive pedigrees. Eleven mutations in GPR56, a gene encoding an evolutionarily dynamic G-protein-coupled receptor, have been identified in 29 patients from 18 families. The clinical features of BFPP include severe mental retardation, motor and language impairment, and epilepsy. No detailed description of the epilepsy is available for the patients reported to date. We report three consanguineous families in which four affected individuals with BFPP and GPR56 mutations had Lennox-Gastaut syndrome.
  
  
  METHODS
  Family studies, brain magnetic resonance imaging (MRI), electroencephalography (EEG)-video recordings, and mutation analysis.
  
  
  RESULTS
  In Family 1, with one affected proband, we found an R565W change in the second extracellular loop of GPR56, involving a highly conserved aminoacidic residue. In Family 2, with one affected proband, we found an R79X change affecting the protein N-terminus and predicted to cause a premature truncation with loss of the G-protein-coupled receptor proteolytic site. In family 3, with two affected siblings, we found an R33P substitution in the protein N-terminus, involving a highly conserved aminoacidic residue. Epilepsy, present in all four patients, had started between ages 1 and 8 years, with infantile spasms in one patient and with de novo Lennox-Gastaut syndrome in the remaining three. All patients had Lennox-Gastaut syndrome when last observed, at ages 13 to 32 years.
  
  
  CONCLUSIONS
  Several genes, when mutated, can cause malformations of cortical development that have been associated with the Lennox-Gastaut syndrome. BFPP caused by GPR56 mutations represents an additional, although rare, genetically determined cause of Lennox-Gastaut syndrome.
authors.affiliation: Pediatric Neurology and Neurogenetics Unit, Children's Hospital A. Meyer-University of Florence, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Parrini
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Ferrari
authors.forename: Thomas
authors.initials: T
authors.lastname: Dorn
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Walsh
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000209:etiology / Q000235:genetics / Q000473:pathology; D005192:Family Health; D005260:Female; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology; D007839:Functional Laterality; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications / Q000235:genetics / Q000473:pathology; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D010296:Parietal Lobe / Q000473:pathology / Q000503:physiopathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D055815:Young Adult
chemical_list: C118925:ADGRG1 protein, human; D043562:Receptors, G-Protein-Coupled