title: Compound heterozygosity in GPR56 with bilateral frontoparietal polymicrogyria.
abstract: Polymicrogyria is caused by a diverse etiology, one of which is gene mutation. At present, only one gene (GPR56) is known to cause polymicrogyria, which leads to a distinctive phenotype termed bilateral frontoparietal polymicrogyria (BFPP). BFPP is an autosomal recessive inherited human brain malformation with abnormal cortical lamination. Here, we identified compound heterozygous GPR56 mutations in a patient with BFPP. The proband was a Japanese female born from non-consanguineous parents. She presented with mental retardation, developmental motor delay, epilepsy exhibiting the feature of Lennox-Gastaut syndrome, exotropia, bilateral polymicrogyria with a relatively spared perisylvian region, bilateral patchy-white-matter MRI signal changes, and hypoplastic pontine basis. GPR56 sequence analysis revealed a c.107G>A substitution leading to a p.S36N, and a c.113G>A leading to a p.R38Q. Although affected individuals with compound heterozygosity in GPR56 have not been previously described, we presume that compound heterozygosity of these two mutations in a ligand binding domain within the extracellular N-terminus of protein could result in BFPP. In addition, we observed unusually less involvement of perisylvian cortex for polymicrogyria, and Lennox-Gastaut syndrome for epilepsy, which are likely common features in patients with BFPP caused by GPR56 mutations.
authors: Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan. Electronic address: yujinn0728@ybb.ne.jp.
authors: Yuji
authors: Y
authors: Fujii
authors: Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan.
authors: Nobutsune
authors: N
authors: Ishikawa
authors: Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan.
authors: Yoshiyuki
authors: Y
authors: Kobayashi
authors: Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan.
authors: Masao
authors: M
authors: Kobayashi
authors: Department of Pediatrics, Yamagata University, Faculty of Medicine, Yamagata, Japan.
authors: Mitsuhiro
authors: M
authors: Kato
mesh_terms: D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002648:Child; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D005260:Female; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D054220:Malformations of Cortical Development / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: C118925:ADGRG1 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: GPR56; Heterozygous mutation; Lennox–Gastaut; Polymicrogyria