Bilateral frontoparietal polymicrogyria, Lennox-Gastaut syndrome, and GPR56 gene mutations

Elena Parrini, Anna Rita Ferrari, Thomas Dorn, Christopher A. Walsh, Renzo Guerrini

Research output: Contribution to journalArticle

Abstract

Purpose: 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. Discussion: 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.

Original languageEnglish
Pages (from-to)1344-1353
Number of pages10
JournalEpilepsia
Volume50
Issue number6
DOIs
Publication statusPublished - Jun 2009

Fingerprint

Mutation
Genes
Epilepsy
G-Protein-Coupled Receptors
Infantile Spasms
Malformations of Cortical Development
Video Recording
Pedigree
Intellectual Disability
Lennox Gastaut Syndrome
Bilateral Frontoparietal Polymicrogyria
Siblings
Electroencephalography
Proteins
Language
Magnetic Resonance Imaging
Brain

Keywords

  • Epilepsy
  • GPR56
  • Lennox-Gastaut
  • Polymicrogyria

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Bilateral frontoparietal polymicrogyria, Lennox-Gastaut syndrome, and GPR56 gene mutations. / Parrini, Elena; Ferrari, Anna Rita; Dorn, Thomas; Walsh, Christopher A.; Guerrini, Renzo.

In: Epilepsia, Vol. 50, No. 6, 06.2009, p. 1344-1353.

Research output: Contribution to journalArticle

Parrini, Elena ; Ferrari, Anna Rita ; Dorn, Thomas ; Walsh, Christopher A. ; Guerrini, Renzo. / Bilateral frontoparietal polymicrogyria, Lennox-Gastaut syndrome, and GPR56 gene mutations. In: Epilepsia. 2009 ; Vol. 50, No. 6. pp. 1344-1353.
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