Xp11.22 Microduplications Including HUWE1: Case Report and Literature Review

Sonia Orivoli; Elena Pavlidis; Gaetano Cantalupo; Marianna Pezzella; Federico Zara; Livia Garavelli; Francesco Pisani; Benedetta Piccolo

doi:10.1055/s-0035-1566233

Neuropediatrics, Inhaltsverzeichnis

Neuropediatrics 2016; 47(01): 051-056
DOI: 10.1055/s-0035-1566233

Short Communication

Georg Thieme Verlag KG Stuttgart · New York

Xp11.22 Microduplications Including HUWE1: Case Report and Literature Review

Authors

Sonia Orivoli

¹Child Neuropsychiatry Unit, Department of Neuroscience, University-Hospital of Parma, Parma, Italy
Elena Pavlidis

¹Child Neuropsychiatry Unit, Department of Neuroscience, University-Hospital of Parma, Parma, Italy
Gaetano Cantalupo

²Child Neuropsychiatry Unit, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy
Marianna Pezzella

³Muscular and Neurodegenerative Disease Unit, Institute G. Gaslini, Genova, Italy
Federico Zara

³Muscular and Neurodegenerative Disease Unit, Institute G. Gaslini, Genova, Italy
Livia Garavelli

⁴Clinical Genetics Unit, IRCCS, S. Maria Nuova Hospital, Reggio Emilia, Italy
Francesco Pisani

¹Child Neuropsychiatry Unit, Department of Neuroscience, University-Hospital of Parma, Parma, Italy
Benedetta Piccolo

⁵Child Neuropsychiatry Unit, Mother and Child Department, University-Hospital of Parma, Parma, Italy

Abstract

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.

Keywords

intellectual disability - HUWE1 - X-linked - EEG abnormalities

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Referenzen

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