TY - JOUR
T1 - Xp11.22 Microduplications Including HUWE1
T2 - Case Report and Literature Review
AU - Orivoli, Sonia
AU - Pavlidis, Elena
AU - Cantalupo, Gaetano
AU - Pezzella, Marianna
AU - Zara, Federico
AU - Garavelli, Livia
AU - Pisani, Francesco
AU - Piccolo, Benedetta
N1 - Georg Thieme Verlag KG Stuttgart · New York.
PY - 2016/1
Y1 - 2016/1
N2 - 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.
AB - 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.
KW - Child
KW - Chromosomes, Human, X
KW - Electroencephalography
KW - Humans
KW - Intellectual Disability
KW - Magnetic Resonance Imaging
KW - Male
KW - Mutation
KW - Ubiquitin-Protein Ligases
KW - Case Reports
KW - Journal Article
KW - Review
U2 - 10.1055/s-0035-1566233
DO - 10.1055/s-0035-1566233
M3 - Article
C2 - 26587761
VL - 47
SP - 51
EP - 56
JO - Neuropediatrics
JF - Neuropediatrics
SN - 0174-304X
IS - 1
ER -