Psychiatric Genetics最新文献

Patients carrying 22q13.33 duplication present variable neurodevelopmental phenotype. Among these, patients with genetic alteration disrupting SHANK3 gene are very rare and they also present neurodevelopmental disorder such as autism spectrum disorder and intellectual disability. The real incidence is unknown because mild and variable phenotype could cause reduction in diagnosed cases. We describe the first case of 22q13.33 microduplication disrupting SHANK3 gene, inherited from mother to son, that presents a "persistent" language and speech sound disorder as main symptom without intellectual disability and autism spectrum disorder. More clinical reports with accurate phenotype description are needed to better define the profile of carriers of this genetic alteration.

Maternal 15q11.2-q13.1 duplication syndrome is associated with a variety of developmental and neuropsychiatric abnormalities. Although schizophrenia-like presentations have been reported, details pertaining to the nature of the corresponding psychotic symptoms and their response to treatment have only been described in a few cases, and no reviews summarizing the literature currently exist. As such, we describe a new case of 15q11.2-q13.1 duplication syndrome-associated schizoaffective disorder and also performed a systematic review of the literature. Our patient's presentation is somewhat unique as she experienced visual hallucinations in the absence of auditory hallucinations. This is also the first report to describe full symptomatic remission in response to relatively low-dose atypical antipsychotic therapy.

KCNQ2 mutations are a common cause of early-onset epileptic syndromes. They are associated with heterogeneous developmental profiles, from mild to severe cognitive and social impairments that need better characterization. We report a case of an inherited KCNQ2 mutation due to a deletion c.402delC in a heterozygous state, in the exon 3 of the KCNQ2 gene. A 5-year-old boy presented a cluster of sudden-onset generalized tonic-clonic seizures at three months of age, after an unremarkable postnatal period. Multiplex ligation-dependent probe amplification identified a familial mutation after an investigation in the family revealed that this mutation was present on the father's side. The patient was diagnosed with autism and intellectual deficiency in a context of KCNQ2 -encephalopathy. We describe his clinical features in light of current literature. This report highlights the importance of appropriate genetic counseling and psychiatric assessment in planning the medical and social follow-up of a disorder with complex socio-behavioral features.

White-Sutton Syndrome is one of the rare neurodevelopmental disorder inherited in an autosomal dominant manner, mainly caused by de novo mutations in the POGZ gene and shows many phenotypic signs such as intellectual disability, Autism Spectrum Disorder and other spectra. About 70 patients with this syndrome have been reported worldwide. In this paper, we have described different phenotypic features of the White-Sutton Syndrome with a brief review of recent literatures. Finally, we have reported an Iranian male with intellectual disability and visual impairment. We have explained the clinical symptoms of the patient and have compared the patient's phenotype with existing data from individuals with White-Sutton Syndrome. The results of Whole Exome Sequencing test, performed for the patient, declared the presence of a de novo mutation in POGZ gene and confirmed the White-Sutton Syndrome diagnosis.

Introduction: Huntington's disease (HD) stands as an inherited and progressive neurodegenerative ailment distinguished by chorea-esque movement patterns, which manifest as archetypal symptoms. The presence of pronounced psychiatric onset symptoms in patients can considerably amplify the intricacies of accurate diagnosis.

Case presentation: A 43-year-old gentleman was admitted with a five-year chronicle of delusions, hallucinations, and irritability. He had previously received a diagnosis of schizophrenia and had been subjected to a regimen of antipsychotic medications for a span exceeding four years. However, subsequent to the application of cerebral MRI and genetic testing, his condition was conclusively redetermined as HD.

Conclusion: The salient attribute of this case resides in the deferred diagnosis of HD attributable to the presence of acute psychiatric initial symptoms, a scenario bearing noteworthy ramifications for disease oversight and prognostication. This instance warrants attentive scrutiny and discourse within the professional community.

Achondroplasia and autism spectrum disorder (ASD) are two genetically based disorders. The coexistence of autism with chromosomal abnormalities such as Down syndrome, monogenic syndromes such as tuberous sclerosis, Fragile X, and Rett syndrome, and microdeletion syndromes such as Phelan-McDermid syndrome helps to shed light on the genetic basis of autism spectrum disorder. The association between ASD and achondroplasia has been reported twice in the literature. In this article, we report Turkish patients who were born as identical twins from IVF pregnancy of 34 and 36-year-old parents, clinically and molecularly diagnosed with achondroplasia, and diagnosed with ASD at the age of 39 months. Our case is the first twin patient with the coexistence of achondroplasia and autism. We discuss environmental and genetic factors contributing to the development of ASD.

Chromatin, a protein-DNA complex, is a dynamic structure that stores genetic information within the nucleus and responds to molecular/cellular changes in its structure, providing conditional access to the genetic machinery. ATP-dependent chromatin modifiers regulate access of transcription factors and RNA polymerases to DNA by either "opening" or "closing" the structure of chromatin, and its aberrant regulation leads to a variety of neurodevelopmental disorders. The chromodomain helicase DNA-binding (CHD) proteins are ATP-dependent chromatin modifiers involved in the organization of chromatin structure, act as gatekeepers of genomic access, and deposit histone variants required for gene regulation. In this review, we first discuss the structural and functional domains of the CHD proteins, and their binding sites, and phosphorylation, acetylation, and methylation sites. The conservation of important amino acids in SWItch/sucrose non-fermenting (SWI/SNF) domains, and their protein and mRNA tissue expression profiles are discussed. Next, we convey the important binding partners of CHD proteins, their protein complexes and activities, and their involvements in epigenetic regulation. We also show the ChIP-seq binding dynamics for CHD1, CHD2, CHD4, and CHD7 proteins at promoter regions of histone genes, as well as several genes that are critical for neurodevelopment. The role of CHD proteins in development is also discussed. Finally, this review provides information about CHD protein mutations reported in autism and neurodevelopmental disorders, and their pathogenicity. Overall, this review provides information on the progress of research into CHD proteins, their structural and functional domains, epigenetics, and their role in stem cell, development, and neurological disorders.

Introduction: While progress has been made in determining the genetic basis of antisocial behaviour, little progress has been made for antisocial personality disorder (ASPD), a condition that often co-occurs with other psychiatric conditions including substance use disorders, attention deficit hyperactivity disorder (ADHD), and anxiety disorders. This study aims to improve the understanding of the genetic risk for ASPD and its relationship with other disorders and traits.

Methods: We conducted a genome-wide association study (GWAS) of the number of ASPD diagnostic criteria data from 3217 alcohol-dependent participants recruited in the UK (UCL, N = 644) and the USA (Yale-Penn, N = 2573).

Results: We identified rs9806493, a chromosome 15 variant, that showed a genome-wide significant association ( Z -score = -5.501, P = 3.77 × 10 -8 ) with ASPD criteria. rs9806493 is an eQTL for SLCO3A1 (Solute Carrier Organic Anion Transporter Family Member 3A1), a ubiquitously expressed gene with strong expression in brain regions that include the anterior cingulate and frontal cortices. Polygenic risk score analysis identified positive correlations between ASPD and smoking, ADHD, depression traits, and posttraumatic stress disorder. Negative correlations were observed between ASPD PRS and alcohol intake frequency, reproductive traits, and level of educational attainment.

Conclusion: This study provides evidence for an association between ASPD risk and SLCO3A1 and provides insight into the genetic architecture and pleiotropic associations of ASPD.

Autosomal dominant sleep-related hypermotor epilepsy is a rare disease caused by pathogenic variants of CHRNB2, CHRNA4, and CHRNA2 genes, with nocturnal frontal lobe epilepsy as the main symptoms. Syntaxin binding protein 1 (STXBP1) gene mutation can cause developmental and epileptic encephalopathy 4, mainly presenting as a developmental and epileptic encephalopathy. We performed the exome-targeted next-generation sequencing in our patient and identified two heterozygous variants: c.963 + 2T>C of STXBP1 and c.520_527delinsTGCTAC (p.R174Cfs*16) of CHRNB2. Molecular analysis was performed of the variant c.963 + 2T>C. Aberrantly spliced products were observed, proving the pathogenicity of this variant. Refractory seizures and developmental delay could be explained. Although the variant c.520_527delinsTGCTAC could cause the truncation of the proteins, it was ultimately determined to be nonpathogenic. The startle-like responses that occurred occasionally during the night were ultimately determined to be an uncommon phenotype caused by the STXBP1 variant.

Introduction: Post-traumatic stress disorder (PTSD), is associated with an elevated risk of neurodegenerative disorders, but the molecular mechanism was not wholly identified. Aberrant methylation status and miRNA expression pattern have been identified to be associated with PTSD, but their complex regulatory networks remain largely unexplored.

Methods: The purpose of this study was to identify the key genes/pathways related to neurodegenerative disorder development in PTSD by evaluating epigenetic regulatory signature (DNA methylation and miRNA) using an integrative bioinformatic analysis. We integrated DNA expression array data with miRNA and DNA methylation array data - obtained from the GEO database- to evaluate the epigenetic regulatory mechanisms.

Results: Our results indicated that target genes of dysregulated miRNAs were significantly related to several neurodegenerative diseases. Several dysregulated genes in the neurodegeneration pathways interacted with some members of the miR-17 and miR-15/107 families. Our analysis indicated that APP/CaN/NFATs signaling pathway was dysregulated in the peripheral blood samples of PTSD. Besides, the DNMT3a and KMT2D genes, as the encoding DNA and histone methyltransferase enzymes, were upregulated, and DNA methylation and miRNA regulators were proposed as critical molecular mechanisms. Our study found dysregulation of circadian rhythm as the CLOCK gene was upregulated and hypomethylated at TSS1500 CpGs S_shores and was also a target of several dysregulated miRNAs.

Conclusion: In conclusion, we found evidence of a negative feedback loop between stress oxidative, circadian rhythm dysregulation, miR-17 and miR-15/107 families, some essential genes involved in neuronal and brain cell health, and KMT2D/DNMT3a in the peripheral blood samples of PTSD.