Genetics and Psychopathology in the 22q11 Deletion Syndrome

13:12 EDT 31st October 2014 | BioPortfolio

Summary

The purposes of this study are to:

1. study the nature and longitudinal course of psychiatric symptoms in children with the 22q11.2 deletion syndrome and

2. identify genes that contribute to the occurrence of these symptoms.

Description

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.

METHODS.

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.

Study Design

Observational Model: Defined Population, Observational Model: Natural History, Time Perspective: Longitudinal, Time Perspective: Prospective

Conditions

Chromosome 22q11.2 Deletion Syndrome

Location

Children's Hospital of Philadelphia, Dpt of Genetics and Dpt of Child and Adolescent Psychiatry
Philadelphia
Pennsylvania
United States
19104

Status

Recruiting

Source

UMC Utrecht

Results (where available)

View Results

Links

Clinical Trials [453 Associated Clinical Trials listed on BioPortfolio]

Examining Genetic Factors That Affect the Severity of 22q11.2 Deletion Syndrome

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...

Genetic Modifiers for 22q11.2 Syndrome

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...

Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes

OBJECTIVES: I. Investigate phenotype and genotype correlations in patients with Smith-Magenis syndrome (SMS) associated with del(17p11.2). II. Clinically evaluate SMS patients with unusua...

Immunologic Evaluation in Patients With DiGeorge Syndrome or Velocardiofacial Syndrome

OBJECTIVES: I. Determine the pattern of immunologic reconstitution in patients with T-cell compromise due to DiGeorge syndrome or velocardiofacial syndrome. II. Determine any cor...

Non-Invasive Determination of Fetal Chromosome Abnormalities

The overall significance of this study is to develop a laboratory developed test (LDT) to use a new marker in the maternal blood to better identify pregnancies that have a child with a chr...

PubMed Articles [7530 Associated PubMed Articles listed on BioPortfolio]

Identifying patterns of anxiety and depression in children with chromosome 22q11.2 deletion syndrome: Comorbidity predicts behavioural difficulties and impaired functional communications.

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a complex genetic disorder with a variable clinical presentation that can include cardiac, neural, immunological, and psychological issues. Previous...

HIC2 is a Novel Dosage-Dependent Regulator of Cardiac Development Located Within the Distal 22q11 Deletion Syndrome Region.

22q11 deletion syndrome arises from recombination between low copy repeats on chromosome 22. Typical deletions result in hemizygosity for TBX1 associated with congenital cardiovascular disease. Deleti...

Conotruncal malformations and absent thymus due to a deleterious NKX2-6 mutation.

Truncus arteriosus (TA) accounts for ∼1% of congenital heart defects. The aetiology of isolated TA is largely unknown but when occurring as part of a syndrome, it is mostly associated with chromosom...

Association between autism spectrum disorder in individuals with velocardiofacial (22q11.2 deletion) syndrome and PRODH and COMT genotypes.

Velocardiofacial (VCFS; 22q11.2 deletion) syndrome is a genetic disorder that results from a hemizygous deletion of the q11.2 region on chromosome 22, and is associated with greatly increased risk for...

Molecular Screening for 22Q11.2 Deletion Syndrome in Patients With Congenital Heart Disease.

Few studies have investigated the prevalence of 22q11.2 deletion syndrome (22q11.2DS) among patients with isolated heart defects or nonconotruncal heart defects. Polymerase chain reaction (PCR) follow...

Medical and Biotech [MESH] Definitions

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.

More From BioPortfolio on "Genetics and Psychopathology in the 22q11 Deletion Syndrome"

Search BioPortfolio:
Loading
Advertisement

Relevant Topics

Psychiatry
Latest News Clinical Trials Research Drugs Reports Corporate
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
Latest News Clinical Trials Research Drugs Reports Corporate
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
Latest News Clinical Trials Research Drugs Reports Corporate
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...

Advertisement