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De novo 5q14.3 translocation 121.5‐kb upstream of MEF2C in a patient with severe intellectual disability and early‐onset epileptic encephalopathy
Author(s) -
Saitsu Hirotomo,
Igarashi Noboru,
Kato Mitsuhiro,
Okada Ippei,
Kosho Tomoki,
Shimokawa Osamu,
Sasaki Yuki,
Nishiyama Kiyomi,
Tsurusaki Yoshinori,
Doi Hiroshi,
Miyake Noriko,
Harada Naoki,
Hayasaka Kiyoshi,
Matasumoto Naomichi
Publication year - 2011
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.34289
Subject(s) - chromosomal translocation , epilepsy , intellectual disability , breakpoint , encephalopathy , global developmental delay , epileptic spasms , hypsarrhythmia , biology , hypotonia , mef2c , genetics , medicine , pediatrics , psychology , neuroscience , gene , phenotype , gene expression
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. © 2011 Wiley Periodicals, Inc.