Chromosome 22q11.2 Deletion Syndrome Clinical Trial
Official title:
Genetics and Psychopathology in the 22q11 Deletion Syndrome
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.
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.
;
Observational Model: Defined Population, Time Perspective: Longitudinal
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Enrolling by invitation |
NCT03836300 -
Parent and Infant Inter(X)Action Intervention (PIXI)
|
N/A |