Early infantile epileptic encephalopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2)

Am J Med Genet A. 2012 Jan;158A(1):199-205. doi: 10.1002/ajmg.a.34363. Epub 2011 Nov 21.

Abstract

We report on a female patient with early infantile epileptic encephalopathy and severe psychomotor disability possessing a de novo balanced translocation t(1;9)(q32;q13). The patient showed clonic convulsions of extremities 2 days after birth. Electroencephalogram (EEG) transiently showed atypical suppression-burst pattern. The seizures evolved to brief tonic spasms, and hypsarrhythmia on EEG was noticed at age of 5 months, indicating the transition to West syndrome. By using fluorescent in situ hybridization (FISH), southern hybridization, and inverse PCR, the translocation breakpoints were successfully determined at the nucleotide level. The 1q32.1 breakpoint was located within a segmental duplication and disrupted the gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2). The 9q13 breakpoint was suggested to reside in the heterochromatin region. Srgap2 has been shown to be specifically expressed in developing brain of rodents, negatively regulate neuronal migration and induce neurite outgrowth and branching. Thus, SRGAP2 is very likely to play a role in the developing human brain. This is a first report of the SRGAP2 abnormality associated with early infantile epileptic encephalopathy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Brain / abnormalities
  • Child, Preschool
  • Chromosome Mapping
  • Cloning, Molecular
  • Electroencephalography
  • Female
  • GTPase-Activating Proteins / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Segmental Duplications, Genomic
  • Seizures / genetics
  • Spasms, Infantile / genetics*

Substances

  • GTPase-Activating Proteins
  • SRGAP2 protein, human

Supplementary concepts

  • Infantile Epileptic-Dyskinetic Encephalopathy