Mafalda Luce Center for Pervasive Developmental Disorders

Milano, Italy

Mafalda Luce Center for Pervasive Developmental Disorders

Milano, Italy
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Lintas C.,Biomedical University of Rome | Picinelli C.,Mafalda Luce Center for Pervasive Developmental Disorders | Piras I.S.,Mafalda Luce Center for Pervasive Developmental Disorders | Sacco R.,Biomedical University of Rome | And 3 more authors.
Molecular Syndromology | Year: 2015

A novel 19.98-Mb duplication in chromosome Xp22.33p22.12 was detected by array CGH in a 30-year-old man affected by intellectual disability, congenital hypotonia and dysmorphic features. The duplication encompasses more than 100 known genes. Many of these genes (such as neuroligin 4, cyclin-dependent kinase like 5, and others) have already correlated with X-linked intellectual disability and/or neurodevelopmental disorders. Due to the high number of potentially pathogenic genes involved in the reported duplication, we cannot correlate the clinical phenotype to a single gene. Indeed, we suggest that the resulting clinical phenotype may have arisen from the overexpression and consequent perturbation of fine gene dosage. © 2016 S. Karger AG, Basel.


Persico A.M.,Biomedical University of Rome | Merelli S.,Mafalda Luce Center for Pervasive Developmental Disorders
Key Issues in Mental Health | Year: 2015

Multiple observations indicate that environmental and epigenetic factors play an important role in the emergence of autism spectrum disorders (ASD). Growing ASD incidence rates, the incomplete penetrance of many rare variants linked to autism, and increased exposure to environmental contaminants all strongly support the role of gene × environment interactions in a substantial fraction of autistic patients. Within this framework, genetically susceptible individuals exposed to detrimental environmental factors at critical times during neurodevelopment might undergo disrupted brain morphogenesis, neuronal connectivity, and synaptic functioning consequently yielding ASD. Several teratogenic drugs and prenatal viral infections are able to cause autism in humans, as supported by case reports, cohort studies, and animal models. Moreover, recent studies have shown that some newly identified potential neurotoxicants may negatively affect developmental trajectories, leading to altered cognitive, attentive, behavioral, and motor performances, as well as to systemic abnormalities frequently seen in autistic individuals. A variety of mechanisms are potentially involved, ranging from oxidative and inflammatory brain damage to altered gene expression and impaired signal transduction. More research is needed to thoroughly investigate the effects of these compounds on neurodevelopment, to validate their involvement specifically in ASD, to study gene × environment interactions in potentially susceptible individuals, and to plan targeted prevention strategies. © 2015 S. Karger AG, Basel.


PubMed | Mafalda Luce Center for Pervasive Developmental Disorders and Biomedical University of Rome
Type: Journal Article | Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics | Year: 2016

Rare and common CNVs can contribute to the etiology of neurodevelopmental disorders. One of the recurrent genomic aberrations associated with these phenotypes and proposed as a susceptibility locus is the 15q11.2 BP1-BP2 CNV encompassing TUBGCP5, CYFIP1, NIPA2, and NIPA1. Characterizing by array-CGH a cohort of 243 families with various neurodevelopmental disorders, we identified five patients carrying the 15q11.2 duplication and one carrying the deletion. All CNVs were confirmed by qPCR and were inherited, except for one duplication where parents were not available. The phenotypic spectrum of CNV carriers was broad but mainly neurodevelopmental, in line with all four genes being implicated in axonal growth and neural connectivity. Phenotypically normal and mildly affected carriers complicate the interpretation of this aberration. This variability may be due to reduced penetrance or altered gene dosage on a particular genetic background. We evaluated the expression levels of the four genes in peripheral blood RNA and found the expected reduction in the deleted case, while duplicated carriers displayed high interindividual variability. These data suggest that differential expression of these genes could partially account for differences in clinical phenotypes, especially among duplication carriers. Furthermore, urinary Mg


PubMed | Mafalda Luce Center for Pervasive Developmental Disorders and Biomedical University of Rome
Type: Journal Article | Journal: Molecular syndromology | Year: 2016

A novel 19.98-Mb duplication in chromosome Xp22.33p22.12 was detected by array CGH in a 30-year-old man affected by intellectual disability, congenital hypotonia and dysmorphic features. The duplication encompasses more than 100 known genes. Many of these genes (such as neuroligin 4, cyclin-dependent kinase like 5, and others) have already correlated with X-linked intellectual disability and/or neurodevelopmental disorders. Due to the high number of potentially pathogenic genes involved in the reported duplication, we cannot correlate the clinical phenotype to a single gene. Indeed, we suggest that the resulting clinical phenotype may have arisen from the overexpression and consequent perturbation of fine gene dosage.

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