Introduction Non-suicidal self-injury (NSSI) is a clinical condition defined as intentional, self-inflicted act causing pain or superficial damage without suicidal intents (12-35% of the adolescent community). Several findings show a high correlation between NSSI and impairments in the impulsivity control. Objectives The goal of our study is to evaluate the role of impulsivity in NSSI adolescents, relatively to the inhibitory control, in order to investigate if it can represent a neurocognitive risk factor underlying maladaptive behaviours and which psychopathological dimensions can be associated with this neurobiological process. Methods 30 NNSI inpatients (age range: 12 to 18 years), drug-free, were compared with an age-matched control group, using two behavioural paradigms for the study of inhibitory control: the Stop Signal task and the emotive go/Nogo. Psychopathological traits were evaluated by self-report questionnaires for impulsivity dimensions, suicidality and self-injurious acts. Statistical analyses were performed with SPSS program (p =0.05). Results NSSI patients did not present impairments in the global inhibitory control but they had longer movement times in both paradigms and faster reaction times in the Go/no-go behavioural paradigm. Therefore, NSSI patients tended to be impulsive at an early stage of movement (rapid TR) and have to slow down in a second phase (TM slow) in order to have time to rework the cognitive processes underlying movement. Conclusions The impulsivity dimension is a complex construct that involves multiple interconnected factors. The study of neuro-cognitive and psychopathological aspects and how they are interconnected is necessary to draw new perspectives on the etiopathogenesis of NNSI.

Background and purposeHereditary ataxias are heterogeneous groups of neurodegenerative disorders, characterized by cerebellar syndromes associated with dysarthria, oculomotor and corticospinal signs, neuropathy and cognitive impairment.Recent reports have suggested mutations in the SPG7 gene, causing the most common form of autosomal recessive spastic paraplegia (MIM#607259), as a main cause of ataxias. The majority of described patients were homozygotes or compound heterozygotes for the c.1529C>T (p.Ala510Val) change. We screened a cohort of 895 Italian patients with ataxia for p.Ala510Val in order to define the prevalence and genotype–phenotype correlation of this variant.MethodsWe set up a rapid assay for c.1529C>T using restriction enzyme analysis after polymerase chain reaction amplification. We confirmed the diagnosis with Sanger sequencing.ResultsWe identified eight homozygotes and 13 compound heterozygotes, including two novel variants affecting splicing.Mutated patients showed a pure cerebellar ataxia at onset, evolving in mild spastic ataxia (alternatively) associated with dysarthria (~80% of patients), urinary urgency (~30%) and pyramidal signs (~70%). Comparing homozygotes and compound heterozygotes, we noted a difference in age at onset and Scale for the Assessment and Rating of Ataxia score between the two groups, supporting an earlier and more severe phenotype in compound heterozygotes versus homozygotes.ConclusionsThe SPG7 c.1529C>T (p.Ala510Val) mutants accounted for 2.3% of cerebellar ataxia cases in Italy, suggesting that this variant should be considered as a priority test in the presence of late‐onset pure ataxia. Moreover, the heterozygous/homozygous genotype appeared to predict the onset of clinical manifestation and disease progression.

BackgroundArray-comparative genomic hybridization (array-CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID). AimsIdentification of genomic disorders in DD/ID. Materials and methodsWe performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs. ResultsWe identified non-benign CNVs in 29% of patients. Amongst the pathogenic variants (11%), detected with a yield consistent with the literature, we found rare genomic disorders and CNVs spanning known disease genes. We further identified and discussed 51 cases with likely pathogenic CNVs spanning novel candidate genes, including genes encoding synaptic components and/or proteins involved in corticogenesis. Additionally, we identified two deletions spanning potential Topological Associated Domain (TAD) boundaries probably affecting the regulatory landscape. Discussion and conclusionWe show how phenotypic and genetic analyses of array-CGH data allow unraveling complex cases, identifying rare disease genes, and revealing unexpected position effects.

Chromosomal region 1p22 is deleted in ⩾20% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 ( EVI5) and ribosomal protein L5 ( RPL5) . Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5 , however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression. Interestingly, RPL5 but not EVI5 mRNA levels were significantly lower in relapsed patients responding to bortezomib and; both in newly diagnosed and relapsed patients, bortezomib treatment could overcome their bad prognosis by raising their progression-free survival to equal that of patients with high RPL5 expression. In conclusion, our genetic data restrict the MDR on 1p22 to EVI5 and RPL5 and although the role of these genes in promoting MM progression remains to be determined, we identify RPL5 mRNA expression as a biomarker for initial response to bortezomib in relapsed patients and subsequent survival benefit after long-term treatment in newly diagnosed and relapsed patients.