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Early infantile epileptic encephalopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating

Hirotomo Saitsu1, Hitoshi Osaka, Shirou Sugiyama

  • 1Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Kanazawa-ku, Yokohama, Japan. hsaitsu@yokohama-cu.ac.jp

American Journal of Medical Genetics. Part A
|November 23, 2011
PubMed

Insights

A de novo balanced translocation disrupted the SRGAP2 gene, causing early infantile epileptic encephalopathy and West syndrome in a patient. This finding links SRGAP2 gene abnormalities to severe early-onset epilepsy.

Area of Science:

  • Genetics
  • Neuroscience
  • Developmental Biology

Background:

  • Early infantile epileptic encephalopathy (EIEE) and West syndrome are severe neurodevelopmental disorders with complex genetic underpinnings.
  • Balanced translocations can disrupt gene function, leading to congenital abnormalities and developmental disorders.

Observation:

  • A female infant presented with early infantile epileptic encephalopathy, severe psychomotor disability, and clonic convulsions shortly after birth.
  • Electroencephalogram (EEG) findings evolved from an atypical suppression-burst pattern to hypsarrhythmia, indicative of West syndrome.
  • A de novo balanced translocation, t(1;9)(q32;q13), was identified in the patient.

Findings:

  • Nucleotide-level mapping revealed translocation breakpoints disrupting the SRGAP2 gene at 1q32.1 and a heterochromatic region at 9q13.
  • The Slit-Robo Rho GTPase activating protein 2 (SRGAP2) gene is crucial for neuronal development, regulating migration, neurite outgrowth, and branching.
  • This study is the first to report an SRGAP2 gene abnormality associated with early infantile epileptic encephalopathy.

Implications:

  • The disruption of SRGAP2 due to the translocation is strongly implicated as the cause of the patient's severe neurological phenotype.
  • This finding highlights the critical role of SRGAP2 in human brain development and its potential involvement in other neurodevelopmental disorders.
  • Understanding the functional consequences of SRGAP2 disruption may offer new avenues for diagnosing and potentially treating early-onset epileptic encephalopathies.

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