Severe Mental Retardation, Seizures, and Hypotonia Due to Deletions of MEF2C
Severe Mental Retardation, Seizures, and Hypotonia Due to Deletions of MEF2C
复制标题
DOI：
10.1002/ajmg.b.31071
复制
发表时间：
2010-07-01
影响因子：
2.8
通讯作者：
Stankiewicz, Pawet
中科院分区：
文献类型：
--
作者：
Nowakowska, Beata A.;Obersztyn, Ewa;Stankiewicz, Pawet
我们介绍了4例患者，我们使用临床寡核苷酸阵列比较基因组杂交（CGH）染色体微阵列分析（CMA）发现了涉及MEF2C的5q14.3重叠缺失。在病例1中，CMA发现了一个类似于440kb的缺失，包括MEF2C的前三个外显子，该患者为一名3岁的患者，患有严重的精神运动迟缓，周期性震颤，以及在婴儿期观察到的上肢镜像运动的异常运动模式，肌强直、脑电图异常、癫痫、言语缺失、自闭症行为、磨牙和轻度畸形特征。脑部MRI显示胼胝体轻度变薄，枕叶白质髓鞘形成延迟。在病例2中，在一名患有严重发育迟缓、张力低下和癫痫发作的儿童中发现了类似1.8 Mb的TMEM161B和MEF2C缺失。患者3患有癫痫、强直、胼胝体变薄和发育迟缓，与5q14.3中包括MEF2C和其他5个基因的2.4 Mb缺失相似。在病例4中，在脑MRI上发现了一个类似于5.7 Mb MEF2C和其他5个基因缺失的儿童，该儿童患有下肢强直、顽固性癫痫、严重发育迟缓和胼胝体缩短。这些缺失进一步支持了MEF2C单倍不足是导致严重智力迟钝、癫痫发作和张力低下的原因。我们的研究结果与之前的报告相结合，表明外显子靶向寡核苷酸阵列CGH在识别外显子拷贝数变异方面更有效，与在整个基因组中均匀分布探针的阵列相比，它应该能提高对临床显著缺失和重复的检测。(C) 2010 Wiley-Liss, Inc。
We present four patients, in whom we identified overlapping deletions in 5q14.3 involving MEF2C using a clinical oligonucleotide array comparative genomic hybridization (CGH) chromosomal microarray analysis (CMA). In case 1, CMA revealed an similar to 440 kb deletion encompassing the first three exons of MEF2C in a 3-year-old patient with severe psychomotor retardation, periodic tremor, and an abnormal motor pattern with mirror movement of the upper limbs observed during infancy, hypotonia, abnormal EEG, epilepsy, absence of speech, autistic behavior, bruxism, and mild dysmorphic features. MRI of the brain showed mild thinning of the corpus callosum and delay of white matter myelination in the occipital lobes. In case 2, an similar to 1.8 Mb deletion of TMEM161B and MEF2C was found in a child with severe developmental delay, hypotonia, and seizures. Patient 3 had epilepsy, hypotonia, thinning of the corpus callosum, and developmental delay associated with a de novo similar to 2.4 Mb deletion in 5q14.3 including MEF2C and five other genes. In case 4, a de novo similar to 5.7 Mb deletion of MEF2C and five other genes was found in a child with truncal hypotonia, intractable seizures, profound developmental delay, and shortening of the corpus callosum on brain MRI. These deletions further support that haploinsufficiency of MEF2C is responsible for severe mental retardation, seizures, and hypotonia. Our results, in combination with previous reports, imply that exon -targeted oligo array CGH, which is more efficient in identifying exonic copy number variants, should improve the detection of clinically significant deletions and duplications over arrays with probes spaced evenly throughout the genome. (C) 2010 Wiley-Liss, Inc.