title: Early infantile epileptic encephalopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2).
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.
authors: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Kanazawa-ku, Yokohama, Japan. hsaitsu@yokohama-cu.ac.jp
authors: Hirotomo
authors: H
authors: Saitsu
authors: Hitoshi
authors: H
authors: Osaka
authors: Shirou
authors: S
authors: Sugiyama
authors: Kenji
authors: K
authors: Kurosawa
authors: Takeshi
authors: T
authors: Mizuguchi
authors: Kiyomi
authors: K
authors: Nishiyama
authors: Akira
authors: A
authors: Nishimura
authors: Yoshinori
authors: Y
authors: Tsurusaki
authors: Hiroshi
authors: H
authors: Doi
authors: Noriko
authors: N
authors: Miyake
authors: Naoki
authors: N
authors: Harada
authors: Mitsuhiro
authors: M
authors: Kato
authors: Naomichi
authors: N
authors: Matsumoto
mesh_terms: D001483:Base Sequence; D001921:Brain / Q000002:abnormalities; D002675:Child, Preschool; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004569:Electroencephalography; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D056916:Segmental Duplications, Genomic; D012640:Seizures / Q000235:genetics; D013036:Spasms, Infantile / Q000235:genetics*
chemical_list: D020690:GTPase-Activating Proteins; C501995:SRGAP2 protein, human