title: Xp11.22 Microduplications Including HUWE1: Case Report and Literature Review.
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.
authors.affiliation: Child Neuropsychiatry Unit, Department of Neuroscience, University-Hospital of Parma, Parma, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Orivoli
authors.affiliation: Child Neuropsychiatry Unit, Department of Neuroscience, University-Hospital of Parma, Parma, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pavlidis
authors.affiliation: Child Neuropsychiatry Unit, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Cantalupo
authors.affiliation: Muscular and Neurodegenerative Disease Unit, Institute G. Gaslini, Genova, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Pezzella
authors.affiliation: Muscular and Neurodegenerative Disease Unit, Institute G. Gaslini, Genova, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.affiliation: Clinical Genetics Unit, IRCCS, S. Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Garavelli
authors.affiliation: Child Neuropsychiatry Unit, Department of Neuroscience, University-Hospital of Parma, Parma, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pisani
authors.affiliation: Child Neuropsychiatry Unit, Mother and Child Department, University-Hospital of Parma, Parma, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Piccolo
mesh_terms: D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics*; D004569:Electroencephalography; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; C502830:HUWE1 protein, human; D044767:Ubiquitin-Protein Ligases