schizophrenia and inherited disease

The mammalian genome undergoes two global epigenetic reprogramming events during the establishment of primordial germ cells and in the pre-implantation embryo after fertilization. These events involve the erasure and re-establishment of DNA methylation marks. However, imprinted genes and transposable elements (TEs) maintain their DNA methylation signatures to ensure normal embryonic development and genome stability. Despite extensive research in mice and humans, there is limited knowledge regarding environmentally induced epigenetic marks that escape epigenetic reprogramming in other species...

In 1939, Hans Luxenburger published a detailed overview of the current status of schizophrenia genetics research, reaching six major conclusions. First, schizophrenia is clearly a hereditary disease. Second, however, schizophrenia is not the hereditary trait itself but rather the consequences of a slowly developing biological progress, the nature of which remains entirely unknown. Third, the full manifestation of the disorder requires certain environmental influences that must come into play. In around 30% of cases, the environment can inhibit hereditary factors so that the predisposition does not manifest in schizophrenia...

The intestinal flora has been the focus of numerous investigations recently, with inquiries not just into the gastrointestinal aspects but also the pathomechanism of other diseases such as nervous system disorders and mitochondrial diseases. Mitochondrial disorders are the most common type of inheritable metabolic illness caused by mutations of mitochondrial and nuclear DNA. Despite the intensive research, its diagnosis is usually difficult, and unfortunately, treating it challenges physicians. Metabolites of the kynurenine pathway are linked to many disorders, such as depression, schizophrenia, migraine, and also diseases associated with impaired mitochondrial function...

Changes in the nervous system are related to a wide range of mental disorders, which include neurodevelopmental disorders (NDD) that are characterized by early onset mental conditions, such as schizophrenia and autism spectrum disorders and correlated conditions (ASD). Previous studies have shown distinct genetic components associated with diverse schizophrenia and ASD phenotypes, with mostly focused on rescuing neural phenotypes and brain activity, but alterations related to vision are overlooked. Thus, as the vision is composed by the eyes that itself represents a part of the brain, with the retina being formed by neurons and cells originating from the glia, genetic variations affecting the brain can also affect the vision...

Schizophrenia (SCZ) is influenced by a combination of genetic and environmental factors. Although several studies have been conducted to identify the causative loci and genes, few of these loci or genes can be repeated due to the high phenotypic and genetic heterogeneity of disease, and their mechanisms are not fully understood. There may be some "missing heritability" that has not yet been found. In order to investigate the deleterious heritable mutations, whole-exome sequencing (WES) in pedigrees with SCZ was used in the current work...

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...

Phosphodiesterase 2 A (PDE2A) is an enzyme involved in the homeostasis of cAMP and cGMP and is the most highly expressed PDE in human brain regions critical for socio-cognitive behavior. In cerebral cortex and hippocampus, PDE2A expression level is upregulated in Fmr1-KO mice, a model of the Fragile X Syndrome (FXS), the most common form of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Indeed, PDE2A translation is negatively modulated by FMRP, whose functional absence causes FXS...

Approximately half of the human genome includes repetitive sequences, and these DNA sequences (as well as their transcribed repetitive RNA and translated amino-acid repeat sequences) are known as the repeatome. Within this repeatome there are a couple of million tandem repeats, dispersed throughout the genome. These tandem repeats have been estimated to constitute ∼8% of the entire human genome. These tandem repeats can be located throughout exons, introns and intergenic regions, thus potentially affecting the structure and function of tandemly repetitive DNA, RNA and protein sequences...

The forces of evolution-mutation, selection, migration, and genetic drift-shape the genetic architecture of human traits, including the genetic architecture of complex neuropsychiatric illnesses. Studying these illnesses in populations that are diverse in genetic ancestry, historical demography, and cultural history can reveal how evolutionary forces have guided adaptation over time and place. A fundamental truth of shared human biology is that an allele responsible for a disease in anyone, anywhere, reveals a gene critical to the normal biology underlying that condition in everyone, everywhere...

Schizophrenia is a severe psychological disorder in which reality is interpreted abnormally by the patient. The symptoms of the disease include delusions and hallucinations, associated with extremely disordered behavior and thinking, which may affect the daily lives of the patients. Advancements in technology have led to understanding the dynamics of the disease and the identification of the underlying causes. Multiple investigations prove that it is regulated genetically, and epigenetically, and is affected by environmental factors...

INTRODUCTION: Leigh syndrome (LS) is a mitochondrial disease characterized by subacute necrotizing encephalomyelopathy with an estimated incidence of 1:40,000 births. The comorbidity of psychotic symptoms noted in mitochondrial and psychiatric diseases has spurred interest in the effects of DNA mutations and psychiatric disorders. Case presentation . We report the case of a Tunisian 28-year-old male diagnosed with maternally inherited Leigh syndrome. He presented anxiety and auditory hallucinations, and he reported a vague, unsystematized delusion evolving since 6 months...

We report a 20-year-old, female, adopted Indian patient with over 662 Mb regions of homozy-gosity who presented with intellectual disability, ataxia, schizophrenia, retinal dystrophy, moder-ate-to-severe progressive sensorineural hearing loss (SNHL), congenital hypothyroidism, cleft mi-tral valve with mild mitral valve regurgitation, and dysmorphic features. Exome analysis first on a clinical basis and subsequently on research reanalysis uncovered pathogenic variants in three nu-clear genes following two modes of inheritance that were causal to her complex phenotype...

Fahr's disease is a rare disorder characterized by abnormal calcium deposition within the basal ganglia, cerebellar dentate nuclei, and white matter tracts with subsequent atrophy. Typical CT imaging features include extensive symmetric calcification involving the basal ganglia and subcortical white matter. Primary Fahr's disease (also known as primary familial brain calcification) is diagnosed based on the exclusion of secondary causes such as underlying metabolic or endocrine disorders. The disease may or may not feature a detectable genetic component, which is inherited in an autosomal dominant or recessive pattern...

Schizophrenia (SZ) is a highly inherited disease that affects ~0.5% of the population. The genetic and environmental factors are involved in its aetiology and they interact with each other. Combination of symptoms is unique to each patient, the disease seriously interferes with the ability to function in society and affects the mental state of the patient. In most patients, the first manifestations of SZ appear during the adolescence or early adulthood. The hypothesis that SZ origin in impaired development of the nervous system is currently widely accepted...

Schizophrenia (SZ) is a complex disorder with a highly polygenic inheritance. It can be conceived as the extreme expression of a continuum of traits that are present in the general population often broadly referred to as schizotypy. However, it is still poorly understood how these traits overlap genetically with the disorder. We investigated whether polygenic risk for SZ is associated with these disorder-related phenotypes (schizotypy, psychotic-like experiences, and subclinical psychopathology) in a sample of 253 non-clinically identified participants...

Polygenic risk scores (PRS) are promising for identifying common variant-related inheritance for psychiatric conditions but their integration into clinical practice depends on their clinical utility and psychiatrists' understanding of PRS. Our online survey explored these issues with 276 professionals working in psychiatric genetics (RR: 19%). Overall, participants demonstrated knowledge of how to interpret PRS results. Their performance on knowledge-based questions was positively correlated with participants' self-reported familiarity with PRS (r = 0...

The PARK2 gene is located on 6q26, encodes ubiquitin-E3- ligase, and is a transcriptional repressor of p53. It contains 12 exons. PARK2 copy number variants has been reported in various types of neurodevelopmental disorders, namely schizophrenia, Parkinson's disease (PD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). In this retrospective study, nine cases (five with microdeletion and four with microduplication) are reported with 6q26 deletion disrupting the PARK2 gene...

The oxytocin receptor (OXTR), encoded by the OXTR gene, is responsible for the signal transduction after binding its ligand, oxytocin. Although this signaling is primarily involved in controlling maternal behavior, it was demonstrated that OXTR also plays a role in the development of the nervous system. Therefore, it is not a surprise that both the ligand and the receptor are involved in the modulation of behaviors, especially those related to sexual, social, and stress-induced activities. As in the case of every regulatory system, any disturbances in the structures or functions of oxytocin and OXTR may lead to the development or modulation of various diseases related to the regulated functions, which in this case include either mental problems (autism, depression, schizophrenia, obsessive-compulsive disorders) or those related to the functioning of reproductive organs (endometriosis, uterine adenomyosis, premature birth)...

The average age of fathers at first pregnancy has risen significantly over the last decade owing to various variables, including a longer life expectancy, more access to contraception, later marriage, and other factors. As has been proven in several studies, women over 35 years of age have an increased risk of infertility, pregnancy problems, spontaneous abortion, congenital malformations, and postnatal issues. There are varying opinions on whether a father's age affects the quality of his sperm or his ability to father a child...

Childhood-onset schizophrenia (COS) is a rare form of schizophrenia with an onset prior to 13 years of age. Although genetic factors play a role in COS etiology, only a few causal variants have been reported to date. This study presents a diagnostic exome sequencing (ES) in 37 Israeli Jewish families with a proband diagnosed with COS. By implementing a trio/duo ES approach and applying a well-established diagnostic pipeline, we detected clinically significant variants in 7 probands (19 %). These single nucleotide variants and indels were mostly inherited...