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Autism spectrum disorder (ASD) is characterized by multifactorial etiology and high heritability but can be challenging to be diagnosed, especially in cases presenting subthreshold symptoms with no cognitive or language impairment, which may not be identified until adulthood but may occur in family members of subjects with ASD. This study explores the possible correlation between a genomic imbalance and clinical phenotypes in a family case of a proband with ASD, with subjects presenting full-blown or subthreshold ASD and/or mood disorders. Clinical assessments were carried out by means of the Structured Clinical Interview for DSM-5 (SCID-5) disorders, Autism Spectrum Quotient (AQ), Autism Diagnostic Interview–Revised (ADI-R), Autism Diagnostic Observation Schedule Module 2 (ADOS-2), and Adult Autism Subthreshold Spectrum (AdAS Spectrum). The genetic evaluation included array comparative genomic hybridization (array-CGH). The proband was diagnosed with ASD and bipolar disorder type I (BD-I), her twin brothers with ASD and intellectual disability (ID), and her father and sister with BD type II (BD-II) and autism traits. The proband, her father, twin brothers, and older sister showed a microduplication of 350 kb in 20q11.21. In contrast, the proband’s mother did not present the microduplication or any mental disorder. This study reports a microduplication that segregates with family members affected by ASD or autistic traits comorbid in some cases with bipolar disorder, and that has never been reported in healthy subjects. Among the genes harbored in this region, the TM9SF4 gene has been recently implicated in risk for ASD.

Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disease of presenile onset. A better characterization of neurodegenerative disorders has been sought by using tools such as genome-wide association studies (GWAS), where associations between single nucleotide polymorphisms (SNPs) and cognitive profiles could constitute predictive biomarkers for these diseases. However, in FTD, associations between genotypes and cognitive phenotypes are yet to be explored. Here, we evaluate a possible relationship between genetic variants and some cognitive functions in an FTD population.MethodologyA total of 47 SNPs in genes associated with neurodegenerative diseases were evaluated using the Sequenom MassARRAY platform along with their possible relationship with performance in neuropsychological tests in 105 Colombian patients diagnosed with FTD.Results and discussionThe SNPs rs429358 (APOE), rs1768208 (MOBP), and rs1411478 (STX6), were identified as risk factors for having a low cognitive performance in inhibitory control and phonological verbal fluency. Although the significance level was not enough to reach the corrected alpha for multiple comparison correction, our exploratory data may constitute a starting point for future studies of these SNPs and their relationship with cognitive performance in patients with a probable diagnosis of FTD. Further studies with an expansion of the sample size and a long-term design could help to explore the predictive nature of the potential associations we identified.

Introduction: Older-age bipolar disorder (OABD) may involve neurocognitive decline and behavioral disturbances that could share features with the behavioral variant of frontotemporal dementia (bvFTD), making the differential diagnosis difficult in cases of suspected dementia.Objective: To compare the neuropsychological profile, brain morphometry, and structural connectivity patterns between patients diagnosed with bvFTD, patients classified as OABD with an early onset of the disease (EO-OABD), and healthy controls (HC).Methods: bvFTD patients (n = 25, age: 66 ± 7, female: 64%, disease duration: 6 ± 4 years), EO-OABD patients (n = 17, age: 65 ± 9, female: 71%, disease duration: 38 ± 8 years), and HC (n = 28, age: 62 ± 7, female: 64%) were evaluated through neuropsychological tests concerning attention, memory, executive function, praxis, and language. Brain morphometry was analyzed through surface-based morphometry (SBM), while structural brain connectivity was assessed through diffusion tensor imaging (DTI).Results: Both bvFTD and EO-OABD patients showed lower performance in neuropsychological tests of attention, verbal fluency, working memory, verbal memory, and praxis than HC. Comparisons between EO-OABD and bvFTD showed differences limited to cognitive flexibility delayed recall and intrusion errors in the memory test. SBM analysis demonstrated that several frontal, temporal, and parietal regions were altered in both bvFTD and EO-OABD compared to HC. In contrast, comparisons between bvFTD and EO-OABD evidenced differences exclusively in the right temporal pole and the left entorhinal cortex. DTI analysis showed alterations in association and projection fibers in both EO-OABD and bvFTD patients compared to HC. Commissural fibers were found to be particularly affected in EO-OABD. The middle cerebellar peduncle and the pontine crossing tract were exclusively altered in bvFTD. There were no significant differences in DTI analysis between EO-OABD and bvFTD.Discussion: EO-OABD and bvFTD may share an overlap in cognitive, brain morphometry, and structural connectivity profiles that could reflect common underlying mechanisms, even though the etiology of each disease can be different and multifactorial.