title: De novo 5q14.3 translocation 121.5-kb upstream of MEF2C in a patient with severe intellectual disability and early-onset epileptic encephalopathy.
abstract: Recent studies have shown that haploinsufficiency of MEF2C causes severe intellectual disability, epilepsy, hypotonia, and cerebral malformations. We report on a female patient with severe intellectual disability, early-onset epileptic encephalopathy, and hypoplastic corpus callosum, possessing a de novo balanced translocation, t(5;15)(q13.3;q26.1). The patient showed upward gazing and tonic seizure of lower extremities followed by generalized clonic seizures at 4 months of age. Electroencephalogram showed hypsarrhythmia when asleep. By using fluorescent in situ hybridization (FISH), southern hybridization and inverse PCR, the translocation breakpoints were determined at the nucleotide level. The 5q14.3 breakpoint was localized 121.5-kb upstream of MEF2C. The 15q26.2 breakpoint was mapped 119-kb downstream of LOC91948 non-coding RNA. We speculate that the translocation may disrupt the proper regulation of MEF2C expression in the developing brain, resulting in severe intellectual disability and early-onset epileptic encephalopathy.
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. hsaitsu@yokohama-cu.ac.jp
authors: Hirotomo
authors: H
authors: Saitsu
authors: Noboru
authors: N
authors: Igarashi
authors: Mitsuhiro
authors: M
authors: Kato
authors: Ippei
authors: I
authors: Okada
authors: Tomoki
authors: T
authors: Kosho
authors: Osamu
authors: O
authors: Shimokawa
authors: Yuki
authors: Y
authors: Sasaki
authors: Kiyomi
authors: K
authors: Nishiyama
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: Kiyoshi
authors: K
authors: Hayasaka
authors: Naomichi
authors: N
authors: Matasumoto
mesh_terms: D059786:Abnormal Karyotype; D061085:Agenesis of Corpus Callosum / Q000235:genetics; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003001:Cloning, Molecular; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D026161:MADS Domain Proteins / Q000235:genetics* / Q000378:metabolism; D064326:MEF2 Transcription Factors; D008279:Magnetic Resonance Imaging; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D020161:Physical Chromosome Mapping; D022661:RNA, Untranslated / Q000235:genetics; D012640:Seizures / Q000235:genetics / Q000503:physiopathology; D014178:Translocation, Genetic
chemical_list: D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D018006:Myogenic Regulatory Factors; D022661:RNA, Untranslated