D-aspartate oxidase gene duplication induces social recognition memory deficit in mice and intellectual disabilities in humans

The D-aspartate oxidase (DDO) gene encodes the enzyme responsible for the catabolism of D-aspartate, an atypical amino acid enriched in the mammalian brain and acting as an endogenous NMDA receptor agonist. Considering the key role of NMDA receptors in neurodevelopmental disorders, recent findings suggest a link between D-aspartate dysmetabolism and schizophrenia. To clarify the role of D-aspartate on brain development and functioning, we used a mouse model with constitutive Ddo overexpression and D-aspartate depletion. In these mice, we found reduced number of BrdU-positive dorsal pallium neurons during corticogenesis, and decreased cortical and striatal gray matter volume at adulthood. Brain abnormalities were associated with social recognition memory deficit at juvenile phase, suggesting that early D-aspartate occurrence influences neurodevelopmental related phenotypes. We corroborated this hypothesis by reporting the first clinical case of a young patient with severe intellectual disability, thought disorders and autism spectrum disorder symptomatology, harboring a duplication of a chromosome 6 region, including the entire DDO gene

Positive effects of physical activity in autism spectrum disorder: how influences behavior, metabolic disorder and gut microbiota

Autism spectrum disorder is a neurodevelopmental disorder characterized by social interactions and communication skills impairments that include intellectual disabilities, communication delays and self-injurious behaviors; often are present systemic comorbidities such as gastrointestinal disorders, obesity and cardiovascular disease. Moreover, in recent years has emerged a link between alterations in the intestinal microbiota and neurobehavioral symptoms in children with autism spectrum disorder. Recently, physical activity and exercise interventions are known to be beneficial for improving communication and social interaction and the composition of microbiota. In our review we intend to highlight how different types of sports can help to improve communication and social behaviors in children with autism and also show positive effects on gut microbiota composition

Identification of a De Novo Deletion by Using A-CGH Involving PLNAX2: An Interesting Candidate Gene in Psychomotor Developmental Delay

Psychomotor developmental delay is a disorder with a prevalence of 12–18% in the pediatric population, characterized by the non-acquisition of motor, cognitive and communication skills during the child’s development, in relation to chronological age. An appropriate neuropsychomotor evaluation and the use of new technologies, such as Array Comparative Genomic Hybridization (a-CGH) and Next-generation sequencing (NGS), can contribute to early diagnosis and improving the quality of life. In this case, we have analyzed a boy aged 2 years and 8 months, with a diagnosis of psychomotor developmental delay, mainly in the area of communication and language. The a-CGH analysis identified three de novo deletions of uncertain clinical significance, involving PLXNA2 (1q32.2), PRELID2, GRXCR2 and SH3RF2 (5q32), RIMS1 (6q13), and a heterozygous duplication of maternal origin involved three genes: HELZ, PSMD12 and PITPNC1 (17q24.2). Among all these alterations, our attention focused on the PLXNA2 gene because of the central function that plexin 2 carries out in the development of the central nervous system. However, all genes detected in the analysis could contribute to the phenotypic characteristics of the patient

Identification of a De Novo Deletion by Using A-CGH Involving PLNAX2: An Interesting Candidate Gene in Psychomotor Developmental Delay

: Psychomotor developmental delay is a disorder with a prevalence of 12-18% in the pediatric population, characterized by the non-acquisition of motor, cognitive and communication skills during the child's development, in relation to chronological age. An appropriate neuropsychomotor evaluation and the use of new technologies, such as Array Comparative Genomic Hybridization (a-CGH) and Next-generation sequencing (NGS), can contribute to early diagnosis and improving the quality of life. In this case, we have analyzed a boy aged 2 years and 8 months, with a diagnosis of psychomotor developmental delay, mainly in the area of communication and language. The a-CGH analysis identified three de novo deletions of uncertain clinical significance, involving PLXNA2 (1q32.2), PRELID2, GRXCR2 and SH3RF2 (5q32), RIMS1 (6q13), and a heterozygous duplication of maternal origin involved three genes: HELZ, PSMD12 and PITPNC1 (17q24.2). Among all these alterations, our attention focused on the PLXNA2 gene because of the central function that plexin 2 carries out in the development of the central nervous system. However, all genes detected in the analysis could contribute to the phenotypic characteristics of the patient

Combined aCGH and Exome Sequencing Analysis Improves Autism Spectrum Disorders Diagnosis: A Case Report

: Background and Objectives: The development and standardization of genome-wide technologies able to carry out high-resolution, genomic analyses in a cost- and time-affordable way is increasing our knowledge regarding the molecular bases of complex diseases like autism spectrum disorder (ASD). ASD is a group of heterogeneous diseases with multifactorial origins. Genetic factors seem to be involved, albeit they remain still largely unknown. Here, we report the case of a child with a clinical suspicion of ASD investigated by using such a genomic high-resolution approach. Materials and Methods: Both array comparative genomic hybridization (aCGH) and exome sequencing were carried out on the family trio. aCGH was performed using the 4 × 180 K SurePrint G3 Human CGH Microarray, while the Human All Exon V7 targeted SureSelect XT HS panel was used for exome sequencing. Results: aCGH identified a paternally inherited duplication of chromosome 7 involving the CNTNAP2 gene, while 5 potentially clinically-relevant variants were identified by exome sequencing. Conclusions: Within the identified genomic alterations, the CNTNAP2 gene duplication may be related to the patient's phenotype. Indeed, this gene has already been associated with brain development and cognitive functions, including language. The paternal origin of the alteration cannot exclude an incomplete penetrance. Moreover, other genomic factors may act as phenotype modifiers combined with CNTNAP2 gene duplication. Thus, the case reported herein strongly reinforces the need to use extensive genomic analyses to shed light on the bases of complex diseases

The Potential Usefulness of the Expanded Carrier Screening to Identify Hereditary Genetic Diseases: A Case Report from Real-World Data

Expanded carrier screening (ECS) means a comprehensive genetic analysis to evaluate an individual’s carrier status. ECS is becoming more frequently used, thanks to the availability of techniques such as next generation sequencing (NGS) and array comparative genomic hybridization (aCGH), allowing for extensive genome-scale analyses. Here, we report the case of a couple who underwent ECS for a case of autism spectrum disorder in the male partner family. aCGH and whole-exome sequencing (WES) were performed in the couple. aCGH analysis identified in the female partner two deletions involving genes associated to behavioral and neurodevelopment disorders. No clinically relevant alterations were identified in the husband. Interestingly, WES analysis identified in the male partner a pathogenic variant in the LPL gene that is emerging as a novel candidate gene for autism. This case shows that ECS may be useful in clinical contexts, especially when both the partners are analyzed before conception, thus allowing the estimation of their risk to transmit an inherited condition. On the other side, there are several concerns related to possible incidental findings and difficult-to-interpret results. Once these limits are defined by the establishment of specific guidelines, ECS may have a greater diffusion

Athlete's Passport: Prevention of Infections, Inflammations, Injuries and Cardiovascular Diseases

Laboratory medicine in sports medicine is taking on an ever-greater role in the assessment and monitoring of an athlete’s health condition. The acute or intense exercise practiced by elite athletes can lead to the appearance of infections, inflammations, muscle injuries or cardiovascular disorders, whose diagnosis is not always rapid and efficient, as there is no continuous monitoring of the athlete. The absence of such monitoring can have serious consequences in terms of recovery of the professional athlete. These imbalances can induce metabolic adaptations which translate into alterations of specific parameters in terms of concentration and activity. The aim of this study was to follow the variation of specific biochemical biomarkers in a basketball team participating to the maximum championship during different phases of the agonistic season. The evaluation of serum biomarkers can help doctors to safeguard the athlete’s health and sports trainers to adapt workouts, thus avoiding the appearance of diseases and injuries that in some cases can be underestimated by becoming irreversible ailments that do not allow the athlete to return to a healthy state. This information can be useful to create athlete biologic passports

Application of array-CGH analysis in immune-virotherapy approach

Introduction: oncololytic adenoviruses (OAds), viruses constructed to replicate in tumor cells, improve the outcome of cancer therapy in some cases, such as sarcomas. However, the molecular heterogeneity of tumors requires specific and personalized cancer treatments in order to set up more adequate and effective therapies. Methods: by using the array Comparative Genomic Hybridization (array-CGH), a molecular approach method, we aimed to identify chromosomal aberrations or Copy Number Variants (CNVs) in three different tumor cell lines: HCT116, SW872 and A2058 selected for their Coxsackievirus and Adenovirus receptor (CAR) expression profile. Results: the cells showed several duplications of genes involved in replicative Adenovirus cycle (binding, internalization, escape) in the core transport, and in the escape of the viral DNA from the capsid. Conclusion: in this study, our aim was to identify chromosomal alterations in genes involved in the OAd replication cycle process. Array-CGH method could be useful to design a platform for a screening analysis in order to identify mutations that can contribute to oncolytic virotherapy approach generating a personalized strategy for tumor suppression

Dietary Thiols: A Potential Supporting Strategy against Oxidative Stress in Heart Failure and Muscular Damage during Sports Activity

Moderate exercise combined with proper nutrition are considered protective factors against cardiovascular disease and musculoskeletal disorders. However, physical activity is known not only to have positive effects. In fact, the achievement of a good performance requires a very high oxygen consumption, which leads to the formation of oxygen free radicals, responsible for premature cell aging and diseases such as heart failure and muscle injury. In this scenario, a primary role is played by antioxidants, in particular by natural antioxidants that can be taken through the diet. Natural antioxidants are molecules capable of counteracting oxygen free radicals without causing cellular cytotoxicity. In recent years, therefore, research has conducted numerous studies on the identification of natural micronutrients, in order to prevent or mitigate oxidative stress induced by physical activity by helping to support conventional drug therapies against heart failure and muscle damage. The aim of this review is to have an overview of how controlled physical activity and a diet rich in antioxidants can represent a “natural cure” to prevent imbalances caused by free oxygen radicals in diseases such as heart failure and muscle damage. In particular, we will focus on sulfur-containing compounds that have the ability to protect the body from oxidative stress. We will mainly focus on six natural antioxidants: glutathione, taurine, lipoic acid, sulforaphane, garlic and methylsulfonylmethane

Childhood obesity: an overview of laboratory medicine, exercise and microbiome

In the last few years, a significant increase of childhood obesity incidence unequally distributed within countries and population groups has been observed, thus representing an important public health problem associated with several health and social consequences. Obese children have more than a 50% probability of becoming obese adults, and to develop pathologies typical of obese adults, that include type 2-diabetes, dyslipidemia and hypertension. Also environmental factors, such as reduced physical activity and increased sedentary activities, may also result in increased caloric intake and/or decreased caloric expenditure. In the present review, we aimed to identify and describe a specific panel of parameters in order to evaluate and characterize the childhood obesity status useful in setting up a preventive diagnostic approach directed at improving health-related behaviors and identifying predisposing risk factors. An early identification of risk factors for childhood obesity could definitely help in setting up adequate and specific clinical treatments