Orivoli Sonia, Pavlidis Elena, Cantalupo Gaetano, Pezzella Marianna, Zara Federico, Garavelli Livia, Pisani Francesco, Piccolo Benedetta
Child Neuropsychiatry Unit, Department of Neuroscience, University-Hospital of Parma, Parma, Italy.
Child Neuropsychiatry Unit, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
Neuropediatrics. 2016 Jan;47(1):51-6. doi: 10.1055/s-0035-1566233. Epub 2015 Nov 20.
Xp11.22 microduplications have been reported in different patients with X-linked intellectual disability. Comparing the duplicated segments, a minimum region of overlap has been identified. Within this region, only one gene, the HUWE1 gene, coding the E3 ubiquitin protein ligase, turned out to be duplicated in all previously described patients. We provide a review of the literature on this topic, making a comparison not only of genetic aspects, but also of clinical, neurophysiological, and neuroradiological findings. Furthermore, we describe the phenotypic and molecular characterization of a case of intellectual disability in a child carrying one of the smallest Xp11.22 microduplications reported, involving the whole sequence of HUWE1 gene. Unlike previously described cases, our patient's neuroimaging showed abnormal findings; he also experienced one seizure and showed interictal electroencephalogram (EEG) epileptiform abnormalities. Given the fact that HUWE1 duplications and mutations have previously been described in several patients with X-linked cognitive impairment, our findings support the hypothesis that HUWE1 gene might be implicate in the pathogenesis of intellectual disability. Nevertheless, further investigations and a more detailed examination of patients' clinical history are needed to clear up other eventual genotype-phenotype correlations, such as the presence of epilepsy/epileptiform EEG abnormalities.
Xp11.22微重复已在不同的X连锁智力障碍患者中被报道。比较重复片段后，已确定了一个最小重叠区域。在该区域内，只有一个基因，即编码E3泛素蛋白连接酶的HUWE1基因，在所有先前描述的患者中均被重复。我们对该主题的文献进行了综述，不仅比较了遗传方面，还比较了临床、神经生理学和神经放射学的发现。此外，我们描述了一名携带所报道的最小Xp11.22微重复之一的儿童智力障碍病例的表型和分子特征，该微重复涉及HUWE1基因的整个序列。与先前描述的病例不同，我们患者的神经影像学显示有异常发现；他还经历了一次癫痫发作，并显示出发作间期脑电图（EEG）癫痫样异常。鉴于先前在几名X连锁认知障碍患者中已描述了HUWE1重复和突变，我们的发现支持了HUWE1基因可能与智力障碍发病机制有关的假设。然而，需要进一步的研究和对患者临床病史进行更详细的检查，以厘清其他可能的基因型-表型相关性，例如癫痫/癫痫样EEG异常的存在。
