Track topics on Twitter Track topics that are important to you
The purposes of this study are to:
2. identify genes that contribute to the occurrence of these symptoms.
The study of genes that are implicated in various mental diseases is increasingly relevant. The association between a gene and a disease can provide valuable information on how the neurobiology of the brain is altered, by studying the function of the protein encoded by the gene. This information is important for the development of new treatments.
However, the identification of these “disease” genes is difficult, due to the complexity of human behavior and the interaction of multiple genes. Moreover, the human genome consists of approximately 35,000 genes, further complicating the matter.
The situation is simplified when a psychiatric disorder and a genetic anomaly co-occur; assuming a causative relation, one can focus on the implicated genetic region.
The 22q11-deletion syndrome (22q11DS) is an example of this type; this syndrome is caused by a disappearance (“deletion”) of 20-30 genes in a well-defined region on chromosome 22. People with 22q11DS have a high risk of autism and psychosis, therefore one or more genes in the 22q11DS region must be associated with these disorders.
In this study we aim to identify these genes, by carefully studying psychiatric symptoms (and additional parameters of brain functioning) in a large sample of 22q11DS children and subsequently statistically correlate these findings to specific genes within the 22q11DS region. If genes associated with autism and/or psychosis in the 22q11DS population can be found, they may help to understand the underlying neurobiology that cause these diseases, not only in 22q11DS patients but in the general population as well.
The aims of this study are:
1. STUDY NATURE AND DEVELOPMENTAL COURSE OF PSYCHIATRIC SYMPTOMS. To perform a prospective longitudinal follow up study of a sample of children with the 22q11.2 deletion syndrome with specific attention to a) possible predictors for psychosis in psychiatric and neuropsychological profile and b) a possible correlation between autistic symptoms and psychosis.
2. ASSESS THE CORRELATION OF 22q11.2 DELETIONS WITH THE PSYCHOSIS / AUTISTIC PHENOTYPE AND ASSOCIATED ENDOPHENOTYPES: To evaluate whether the size of the deletion and / or polymorphisms at selected candidate genes within the 22q11.2 deleted region contribute to the psychosis and or autistic phenotype or to related psychophysiologic / neuropsychological impairments in 22q11DS.
With regard to aim 1:
A large sample (a final sample size of 100-120 is anticipated) of children with 22q11DS, aged 10 - 20 year, is broadly phenotyped using standard psychiatric assessment methods, intelligence and selected neuropsychological tests as well as psychophysiological assessments. Approximately 4 years after the initial assessment a follow up assessment is planned. Age and IQ matched children without the deletion (or any other apparent genetic abnormality) are used as a control group.
With regard to aim 2:
- Phenotypes: Individuals with a certain endophenotype (“cases” e.g. the presence of autistic symptoms or a decreased Pre Pulse Inhibition or impaired performance on executive tasks) will be compared to children without that particular phenotype (“controls”).
- Genetic analysis:
- Genotyping consists of:
1. assessment of the size of the deletion and
2. genotyping single nucleotide polymorphisms (SNPs) across the deleted genomic region. Genotyping will be performed using approximately 75 previously characterized SNPs, with an increased density of SNPs in the target candidate genes (~3-5 SNPs per candidate gene). In order to determine whether a haplotype and/or variants of genes within region 22q11.2 contribute to the autistic phenotype and related neuro-psychological impairments in patients with the deletion, we will identify DNA polymorphisms using existing databases. We will then genotype patients with the 22q11.2 deletion for the selected polymorphisms and compare the allele frequencies and haplotype combinations in 22q11DS patients with the phenotype (“cases”) to those deleted patients without these findings (“controls”) applying chi-square, Fisher’s exact test, and other statistical genetic methods as appropriate.
Observational Model: Defined Population, Observational Model: Natural History, Time Perspective: Longitudinal, Time Perspective: Prospective
Chromosome 22q11.2 Deletion Syndrome
Children's Hospital of Philadelphia, Dpt of Genetics and Dpt of Child and Adolescent Psychiatry
Published on BioPortfolio: 2014-08-27T03:51:14-0400
22q11.2 deletion syndrome is a genetic disorder that can cause heart defects, facial abnormalities, and developmental and learning disabilities. The severity of the disorder can vary widel...
The purpose of the project is the determination of how the deletion of DNA from chromosome 22 at the q11.2 band causes the phenotypes observed in velo-cardio-facial syndrome (VCFS). In oth...
This study is being conducted to develop and evaluate a cell-free fetal DNA test (Ariosa Test) for non-invasive prenatal detection of 22q11.2 chromosomal deletion or duplication.
Background: The present study aims to identify the mechanisms underlying the deficit in facial emotion recognition reported both in schizophrenia and the 22q11.2 deletion syndrome, and th...
This multi-center prospective observational study is designed to track birth outcomes and perinatal correlates to the Panorama prenatal screening test in the general population among ten t...
The 22q11.2 deletion syndrome (velo-cardio-facial syndrome or DiGeorge syndrome) is the most common known contiguous gene deletion syndrome, and is associated with neurodevelopmental problems and dive...
Congenital heart defect (CHD) is the most common form of birth defects. There is a high association between increased nuchal translucency and CHD in fetuses, and CHD in the antenatal period has a high...
22q11.2DS is the most common microdeletion syndrome in humans, usually associated with speech and language delay (SLD). Approximately 75% of children with 22q11.2 microdeletion have congenital heart m...
22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (CO...
The purpose of this study was to clarify the prevalence, type, severity, and age-dependency of hearing loss in 22q11.2 deletion syndrome.
Condition with a variable constellation of phenotypes due to deletion polymorphisms at chromosome location 22q11. It encompasses several syndromes with overlapping abnormalities including the DIGEORGE SYNDROME, VELOCARDIOFACIAL SYNDROME, and CONOTRUNCAL AMOMALY FACE SYNDROME. In addition, variable developmental problems and schizoid features are also associated with this syndrome. (From BMC Med Genet. 2009 Feb 25;10:16) Not all deletions at 22q11 result in the 22q11deletion syndrome.
Congenital syndrome characterized by a spectrum of malformations including the absence of the THYMUS and PARATHYROID GLANDS resulting in T-cell immunodeficiency and HYPOCALCEMIA. Other features include defects in the outflow tract of the HEART and craniofacial anomalies (velocardiofacial syndrome). Most cases result from a deletion of chromosome 22q11.2 or mutation in the TBX1 gene.
An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 per cent of patients with chronic myelocytic leukemia (LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE).
An infantile syndrome characterized by a cat-like cry, failure to thrive, microcephaly, MENTAL RETARDATION, spastic quadriparesis, micro- and retrognathia, glossoptosis, bilateral epicanthus, hypertelorism, and tiny external genitalia. It is caused by a deletion of the short arm of chromosome 5 (5p-).
Susceptibility of chromosomes to breakage leading to translocation; CHROMOSOME INVERSION; SEQUENCE DELETION; or other CHROMOSOME BREAKAGE related aberrations.
Psychiatry is the study of mental disorders and their diagnosis, management and prevention. Conditions include schizophrenia, severe depression and panic disorders among others. There are pharmaceutical treatments as well as other therapies to help...
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...