MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations
MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations
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DOI：
10.1136/jmg.2009.069732
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Bonneau, D.
中科院分区：
文献类型：
--
作者：
Le Meur, N.;Holder-Espinasse, M.;Bonneau, D.
背景在过去几年里，阵列比较基因组杂交（CGH）技术的应用，大大提高了我们检测综合征型智力低下患者隐性不平衡重排的能力。结果在5例无血缘关系的患者中检测到5q14.3微缺失，缺失范围为216 kb ~ 8.8 Mb。这些患者中的大多数还存在面部畸形特征、癫痫和/或脑畸形。这些5 q14微缺失的最小共同缺失区域仅包括MEF 2C，该基因是已知在脑中作为神经发生效应器起作用的蛋白质，其调节兴奋性突触数量。在一个病人具有相似的表型，MEF 2C无义突变随后identified.Conclusion两者合计，这些结果强烈表明，MEF 2C的单倍不足是负责严重的精神发育迟滞与刻板的运动，癫痫发作和/或脑畸形。
Background Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved our ability to detect cryptic unbalanced rearrangements in patients with syndromic mental retardation.Method Molecular karyotyping of six patients with syndromic mental retardation was carried out using whole-genome oligonucleotide array-CGH.Results 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe mental retardation with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified.Conclusion Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations.