Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Am J Med Genet A. 2011 Nov;155A(11):2879-84. doi: 10.1002/ajmg.a.34289. Epub 2011 Oct 11.
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.
最近的研究表明，MEF2C 杂合性缺失会导致严重的智力障碍、癫痫、肌张力减退和脑畸形。我们报告了一名女性患者，她患有严重的智力障碍、早发性癫痫性脑病和胼胝体发育不良，携带新发平衡易位 t(5;15)(q13.3;q26.1)。该患者在 4 个月大时出现向上凝视和下肢强直发作，随后出现全身阵挛性发作。脑电图显示睡眠时出现高幅失律。通过荧光原位杂交（FISH）、Southern 杂交和反向 PCR，确定了易位的断裂点在核苷酸水平上。5q14.3 断点位于 MEF2C 上游 121.5-kb 处。15q26.2 断点位于非编码 RNA LOC91948 的下游 119-kb 处。我们推测易位可能破坏了 MEF2C 在发育中大脑中的正常表达调控，导致严重的智力障碍和早发性癫痫性脑病。
