Exploration and Characterization of the Phenotypic and Genetic Profile of Patients With Early Onset Schizophrenia Associated With Autism Spectrum Disorder and Their First-degree Relatives (GenAuDiss).
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 111
- 试验地点
- 2
- 主要终点
- characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing standard karyotype
研究概览
简要总结
Early onset schizophrenia "early dissociative disorder" is a rare disorder with a low incidence of approximately (1/5000 to 1/20000). Its link with autism spectrum disorders remains unknown although both are serious neurodevelopmental diseases. As part of the 2011-2013 Interregional hospital Clinical Research program, University Department of Child and Adolescent Psychiatry Pediatric Hospitals of CHU de Nice Lenval identified patients with a complex phenotype characterized by an early schizophrenia associated with autism spectrum disorders and developmental disabilities in mild to moderate. This phenotype could be a new syndrome.
The goal of our project is to define the genetic causes of this phenotype. The technique of high throughput sequencing will be used to obtain the sequence of exomes of these patients and their families. This study will therefore be important to give an accurate diagnosis for patients and their families. Moreover, we believe that this project will identify new genes involved allowing a better understanding of the pathophysiology. Recent studies show the involvement of mutations in several genes (eg NRXN1 and UPF3B) in these different clinical phenotypes. However, the genetic basis of the childhood and early onset schizophrenia are much less well known than those of autism spectrum disorder
详细描述
Introduction: Early-onset Schizophrenia (EOS) is a rare and severe condition displaying early dissociative disorder (i.e., age of onset < 18 years). A higher rate of neurodevelopmental abnormalities is observed in EOS compared to adult onset schizophrenia (AOS). Thus, patients affected by EOS typically present intellectual, learning, communication or neuromotor impairments, as well as attention deficit hyperactivity disorder. Early signs of autism spectrum disorders (ASD) are also found in 30% of patients with EOS.
Cytogenetics abnormalities, including copy number variations (CNVs), are frequent in neurodevelopmental disorders and have been linked to ASD physiopathology. Implicated genes encode proteins playing a role in brain development, synaptic morphology, plasticity and neurogenesis. In addition, an increasing number of genetic abnormalities are shared by EOS and ASD, suggesting that schizophrenia can be considered a neurodevelopmental disorder.
The main objective of the present study is to identify mutations in genes involved in neurodevelopmental pathways in our cohort of patients affected by both EOS and ASD.
Method and analysis: We describe here a multicenter study in a pediatric population named "Exploration and characterization of genetic and phenotypic profile of the 'early dissociative disorder' associated with autism spectrum disorder (GenAuDiss)". The study started in April 2014. The inclusion criteria are: age 7 to 22 years, diagnoses of EOS with co-morbid ASD and IQ > 50; as well as parents and siblings of the included patients.
We perform standardized psychiatric assessments (MINI, K-SADS-PL, PANSS, SANS, TCI 226, and AQ) and neurocognitive evaluations (IQ, TMT A/B, and verbal fluency). Then, we study variants of the coding part of the DNA (exome), using next generation sequencing (NGS) process on trio (mother, father, and child). Divers bio-informatics tools such as RVIS and PolyPhen-2 will be used to prioritize the potential candidate genes. The inclusion period of this study will end in November 2019.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 7 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Of the child:
- •≥ 7 years, <18 (below 7 years the diagnosis of schizophrenia is not possible)
- •Schizophrenia Diagnosis done using the diagnostic tool Kiddie sads
- •Autism Diagnosis done using the diagnostic scale Autism Diagnostic interview (ADI-R)
- •Intelligence quotient (IQ) ≥ 50 at Wechsler Intelligence Scale for Children (WISC) IV abridged version
- •Clinical examination
- •Affiliation to social security
- •Obtaining the authorization of the holders of parental authority
- •Brothers and sisters:
- •Minor or Major
- •Similarly biological parents
- •Clinical examination
- •Affiliation to social security
- •Obtaining the authorization of the holders of parental authority for minors or informed consent for major
- •Biological Parent
- •Clinical examination
- •Affiliation to social security
- •Informed Consent
排除标准
- •Of the child:
- •Children refusing to participate
- •Children without verbal language
- •Brothers and sisters:
- •Children refusing to participate
- •Adults protected by law
- •Refusing to participate
- •Adults are protected by law
结局指标
主要结局
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing standard karyotype
时间窗: inclusion visit
A standard karyotype at a resolution of 300 to 400 bands per haploid lot. It can diagnose numerical anomalies and certain structural abnormalities such as reciprocal translocations, inversions, deletions. A standard karyotype at a resolution of 300 to 400 bands per haploid lot is established initially. It can diagnose numerical anomalies and certain structural abnormalities such as reciprocal translocations, inversions, deletions Big. The pathological nature of these mutations will be stutied on the gene function and reaches its pattern of expression.
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing search CGG
时间窗: inclusion visit
A search of the CGG expansion hypermethylated in the 5 'UTR of the FMR1 gene mutation that causes Fragile X syndrome.
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing whole exome sequencing
时间窗: inclusion visit
Whole Exome Sequencing on trio (mother, father and child); This technology has demonstrated its power in recent years to determine the genetic causes of many rare diseases (Ropers, HH., 2012).
次要结局
- Intensity of positive symptoms of schizophrenia(inclusion visit)
- Personality dimensional test(inclusion visit)
- Co-morbid psychiatric diagnosis(inclusion visit)
- Neurocognitive profile(inclusion visit)
- Evaluation of executive and attentional by the verbal fluency test(inclusion visit)
- Clinical evaluation of autistic symptoms(inclusion visit)