title: Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes.
abstract: Human cerebral cortical polymicrogyria is a heterogeneous disorder, with only one known gene (GPR56) associated with an apparently distinctive phenotype, termed bilateral frontoparietal polymicrogyria (BFPP). To define the range of abnormalities that could be caused by human GPR56 mutations and to establish diagnostic criteria for BFPP, we analyzed the GPR56 gene in a cohort of 29 patients with typical BFPP. We identified homozygous GPR56 mutations in all 29 patients with typical BFPP. The total of 11 GPR56 mutations found represented a variety of distinct founder mutations in various populations throughout the world. In addition, we analyzed five patients with BFPP who did not show GPR56 mutation and found that they define a clinically, radiographically, and genetically distinct syndrome that we termed BFPP2. Finally, we studied seven patients with a variety of other polymicrogyria syndromes including bilateral frontal polymicrogyria, bilateral perisylvian polymicrogyria, and bilateral generalized polymicrogyria. No GPR56 mutation was found in these patients. This study provides a molecular confirmation of the BFPP phenotype and provides the wherewithal for diagnostic screening.
authors.affiliation: Division of Newborn Medicine, Department of Medicine, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Piao
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Chang
authors.forename: Adria
authors.initials: A
authors.lastname: Bodell
authors.forename: Katelyn
authors.initials: K
authors.lastname: Woods
authors.forename: Bruria
authors.initials: B
authors.lastname: Benzeev
authors.forename: Meral
authors.initials: M
authors.lastname: Topcu
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Hadassa
authors.initials: H
authors.lastname: Goldberg-Stern
authors.forename: Laszlo
authors.initials: L
authors.lastname: Sztriha
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: A James
authors.initials: AJ
authors.lastname: Barkovich
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D000328:Adult; D001927:Brain Diseases / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009154:Mutation; D009421:Nervous System Malformations / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: C118925:ADGRG1 protein, human; D043562:Receptors, G-Protein-Coupled