Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era.

ABSTRACT: Schizophrenia is a complex neuropsychiatric disease with documented clinical and genetic heterogeneity, and evidence for neurodevelopmental origins. Driven by new genetic technologies and advances in molecular medicine, there has recently been concrete progress in understanding some of the specific genetic causes of this serious psychiatric illness. In particular, several large rare structural variants have been convincingly associated with schizophrenia, in targeted studies over two decades with respect to 22q11.2 microdeletions, and more recently in large-scale, genome-wide case-control studies. These advances promise to help many families afflicted with this disease. In this review, we critically appraise recent developments in the field of schizophrenia genetics through the lens of immediate clinical applicability. Much work remains in translating the recent surge of genetic research discoveries into the clinic. The epidemiology and basic genetic parameters (such as penetrance and expression) of most genomic disorders associated with schizophrenia are not yet well characterized. To date, 22q11.2 deletion syndrome is the only established genetic subtype of schizophrenia of proven clinical relevance. We use this well-established association as a model to chart the pathway for translating emerging genetic discoveries into clinical practice. We also propose new directions for research involving general genetic risk prediction and counseling in schizophrenia.

SUBMITTER: Costain G

PROVIDER: S-EPMC3492098 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Rett syndrome molecular diagnosis and implications in genetic counseling.

Project description:Rett syndrome is a rare genetic X-linked dominant disorder. This syndrome is the most frequent cause of mental retardation in girls. In the classical form of the disease, the presenting signs and the course of development are characteristic. However clinical diagnosis can be very difficult when the expression is not in the classical form. Mutations in MeCP2 are responsible for 80% of cases. When MeCP2 mutation is found in an index case, genetic counseling is similar to that in other X-linked dominant genetic diseases. However, mutations in this gene can cause a spectrum of atypical forms. On the other hand, other genetic conditions like translocations, sex chromosome numerical anomalies, and mutations in other genes can complicate genetic counseling in this syndrome. We present the first case of molecular diagnosis of Rett syndrome in Iran and discuss the recent developments in its genetic counseling.

| S-EPMC3168138 | biostudies-literature

Molecular genetics and clinical applications for RH.

Project description:Rhesus is the clinically most important protein-based blood group system. It represents the largest number of antigens and the most complex genetics of the 30 known blood group systems. The RHD and RHCE genes are strongly homologous. Some genetic complexity is explained by their close chromosomal proximity and unusual orientation, with their tail ends facing each other. The antigens are expressed by the RhD and the RhCE proteins. Rhesus exemplifies the correlation of genotype and phenotype, facilitating the understanding of general genetic mechanisms. For clinical purposes, genetic diagnostics of Rhesus antigens will improve the cost-effective development of transfusion medicine.

| S-EPMC3042511 | biostudies-literature

Evaluating genetic counseling for individuals with schizophrenia in the molecular age.

Project description:Recent advances in schizophrenia genetics are shedding new light on etiopathogenesis, but issues germane to translation of findings into clinical practice are relatively understudied. We assessed the need for, and efficacy of, a contemporary genetic counseling protocol for individuals with schizophrenia.After characterizing rare copy number variation in a cohort of adults with schizophrenia, we recruited subjects from the majority of individuals who had no clinically relevant structural genetic variant. We used a pre-post study design with longitudinal follow-up to assess both the profile of need and the impact of general genetic counseling on key knowledge-based and psychological factors.Thirty-nine (60.0%) of 65 patients approached actively expressed an interest in the study. At baseline, participants (n = 25) tended to overestimate the risk of familial recurrence of schizophrenia, express considerable concern related to this perceived risk, endorse myths about schizophrenia etiology, and blame themselves for their illness. Postcounseling, there was a significant improvement in understanding of the empiric recurrence risk (P = .0090), accompanied by a decrease in associated concern (P = .0020). There were also significant gains in subjective (P = .0007) and objective (P = .0103) knowledge, and reductions in internalized stigma (P = .0111) and self-blame (P = .0401). Satisfaction with genetic counseling, including endorsement of the need for such counseling (86.4%), was high.These results provide initial evidence of need for, and efficacy of, genetic counseling for individuals with schizophrenia. The findings may help facilitate development of a contemporary genetic counseling process that could optimize outcomes in the nascent field of evidence-based psychiatric genetic counseling.

| S-EPMC3885288 | biostudies-literature

Evaluating genetic counseling for family members of individuals with schizophrenia in the molecular age.

Project description:Myths and concerns about the extent and meaning of genetic risk in schizophrenia may contribute to significant stigma and burden for families. Genetic counseling has long been proposed to be a potentially informative and therapeutic intervention for schizophrenia. Surprisingly, however, available data are limited. We evaluated a contemporary genetic counseling protocol for use in a community mental health-care setting by non-genetics professionals.We used a pre-post study design with longitudinal follow-up to assess the impact of genetic counseling on family members of individuals with schizophrenia, where molecular testing had revealed no known clinically relevant genetic risk variant. We assessed the outcome using multiple measures, including standard items and scales used to evaluate genetic counseling for other complex diseases.Of the 122 family members approached, 78 (63.9%) actively expressed an interest in the study. Participants (n = 52) on average overestimated the risk of familial recurrence at baseline, and demonstrated a significant improvement in this estimate postintervention (P < .0001). This change was associated with an enduring decrease in concern about recurrence (P = .0003). Significant and lasting benefits were observed in other key areas, including increased knowledge (P < .0001) and a decreased sense of stigma (P = .0047). Endorsement of the need for genetic counseling was high (96.1%).These results provide initial evidence of the efficacy of schizophrenia genetic counseling for families, even in the absence of individually relevant genetic test results or professional genetics services. The findings support the integration of contemporary genetic counseling for families into the general management of schizophrenia in the community.

| S-EPMC3885286 | biostudies-literature

Clinical diagnosis and genetic counseling of atypical ataxia‑telangiectasia in a Chinese family.

Project description:Ataxia‑telangiectasia (A‑T) is an autosomal recessive chromosome breakage disorder caused by mutations in the ATM serine/threonine kinase (ATM) gene. Typically, it presents in early childhood with progressive cerebellar dysfunction, accompanied by immunodeficiency and oculocutaneous telangiectasia. In the present study, the clinical and genetic findings of a Chinese family affected with A‑T in two live siblings, the proband (II‑2) and his elder brother (II‑1), as well as a fetus (II‑3) were reported. General health, clinical neurological, electrophysiological (motor and sensory nerve conduction) and magnetic resonance imaging evaluations revealed that patients II‑1 and II‑2 had similar symptoms of ataxia, dysarthria, conjunctival hyperemia and elevated serum α‑fetoprotein, whereas patient II‑1 had earlier A‑T onset at 2 years old and more serious problems with movement and intelligence. Targeted sequencing followed by Sanger sequencing revealed that these two patients carried the compound heterozygotes of a novel nonsense mutation c.5170G>T (p.Glu1724Ter) and a known nonsense mutation c.748C>T (p.Arg250Ter) in the ATM gene. Each mutation was inherited from an asymptomatic parent, which therefore confirmed the diagnosis of A‑T. Given this, proband's mother performed prenatal diagnosis in her third pregnancy. Unfortunately, the fetus had the same causal mutations as its siblings and the pregnancy was terminated. The findings of the present study expanded the mutation spectrum of the ATM gene and may help in understanding the genetic basis of A‑T, in order to guide genetic counseling and prenatal diagnosis.

| S-EPMC6471340 | biostudies-literature

Genetic neurological channelopathies: molecular genetics and clinical phenotypes.

Project description:Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies.

| S-EPMC4717447 | biostudies-literature

Imaging Genetics Towards a Refined Diagnosis of Schizophrenia.

Project description:Current diagnoses of schizophrenia and related psychiatric disorders are classified by phenomenological principles and clinical descriptions while ruling out other symptoms and conditions. Specific biomarkers are needed to assist the current diagnostic system. However, complicated gene and environment interactions induce great disease heterogeneity. This unclear etiology and heterogeneity raise difficulties in distinguishing schizophrenia-related effects. Simultaneously, the overlap in symptoms, genetic variations, and brain alterations in schizophrenia and related psychiatric disorders raises similar difficulties in determining disease-specific effects. Imaging genetics is a unique methodology to assess the impact of genetic factors on both brain structure and function. More importantly, imaging genetics builds a bridge to understand the behavioral and clinical implications of genetics and neuroimaging. By characterizing and quantifying the brain measures affected in psychiatric disorders, imaging genetics is contributing to identifying potential biomarkers for schizophrenia and related disorders. To date, candidate gene analysis, genome-wide association studies, polygenetic risk score analysis, and large-scale collaborative studies have made contributions to the understanding of schizophrenia with the potential to serve as biomarkers. Despite limitations, imaging genetics remains promising as more aggregative, clustering methods and imaging genetics-compatible clinical assessments are employed in future studies. We review imaging genetics' contribution to our understanding of the heterogeneity within schizophrenia and the commonalities across schizophrenia and other diagnostic borders, and we will discuss whether imaging genetics is ready to form its own diagnostic system.

| S-EPMC6639711 | biostudies-literature

Schizophrenia genetics in the genome-wide era: a review of Japanese studies.

Project description:The introduction of the genome-wide association study transformed schizophrenia genetics research and has promoted a genome-wide mindset that has stimulated the development of genomic technology, enabling departures from the traditional candidate gene approach. As result, we have witnessed a decade of major discoveries in schizophrenia genetics and the development of genome-wide approaches to the study of copy number variants. These genomic technologies have primarily been applied in populations of European descent. However, more recently both genome-wide association study and copy number variant studies in Asian populations have begun to emerge. In this invited review, we provide concise summaries of the schizophrenia genome-wide association study and copy number variant literature with specific focus on studies conducted in the Japanese population. When applicable, we compare findings observed in the Japanese population with those found in other populations. We conclude with recommendations for future research in schizophrenia genetics, relevant to Japan and beyond.

| S-EPMC5577232 | biostudies-literature

Dystonia Diagnosis: Clinical Neurophysiology and Genetics.

Project description:Dystonia diagnosis is based on clinical examination performed by a neurologist with expertise in movement disorders. Clues that indicate the diagnosis of a movement disorder such as dystonia are dystonic movements, dystonic postures, and three additional physical signs (mirror dystonia, overflow dystonia, and geste antagonists/sensory tricks). Despite advances in research, there is no diagnostic test with a high level of accuracy for the dystonia diagnosis. Clinical neurophysiology and genetics might support the clinician in the diagnostic process. Neurophysiology played a role in untangling dystonia pathophysiology, demonstrating characteristic reduction in inhibition of central motor circuits and alterations in the somatosensory system. The neurophysiologic measure with the greatest evidence in identifying patients affected by dystonia is the somatosensory temporal discrimination threshold (STDT). Other parameters need further confirmations and more solid evidence to be considered as support for the dystonia diagnosis. Genetic testing should be guided by characteristics such as age at onset, body distribution, associated features, and coexistence of other movement disorders (parkinsonism, myoclonus, and other hyperkinesia). The aim of the present review is to summarize the state of the art regarding dystonia diagnosis focusing on the role of neurophysiology and genetic testing.

| S-EPMC9320296 | biostudies-literature

Pompe disease: pathogenesis, molecular genetics and diagnosis.

Project description:Pompe disease (PD) is a rare autosomal recessive disorder caused by mutations in the GAA gene, localized on chromosome 17 and encoding for acid alpha-1,4-glucosidase (GAA). Currently, more than 560 mutations spread throughout GAA gene have been reported. GAA catalyzes the hydrolysis of α-1,4 and α-1,6-glucosidic bonds of glycogen and its deficiency leads to lysosomal storage of glycogen in several tissues, particularly in muscle. PD is a chronic and progressive pathology usually characterized by limb-girdle muscle weakness and respiratory failure. PD is classified as infantile and childhood/adult forms. PD patients exhibit a multisystemic manifestation that depends on age of onset.Early diagnosis is essential to prevent or reduce the irreversible organ damage associated with PD progression. Here, we make an overview of PD focusing on pathogenesis, clinical phenotypes, molecular genetics, diagnosis, therapies, autophagy and the role of miRNAs as potential biomarkers for PD.

| S-EPMC7467391 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data