Social Responsiveness Scale-aided analysis of the clinical impact of copy number variations in autism.
Neurogenetics
; 12(4): 315-23, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21837366
ABSTRACT
Recent array-based studies have detected a wealth of copy number variations (CNVs) in patients with autism spectrum disorders (ASD). Since CNVs also occur in healthy individuals, their contributions to the patient's phenotype remain largely unclear. In a cohort of children with symptoms of ASD, diagnosis of the index patient using ADOS-G and ADI-R was performed, and the Social Responsiveness Scale (SRS) was administered to the index patients, both parents, and all available siblings. CNVs were identified using SNP arrays and confirmed by FISH or array CGH. To evaluate the clinical significance of CNVs, we analyzed three families with multiple affected children (multiplex) and six families with a single affected child (simplex) in which at least one child carried a CNV with a brain-transcribed gene. CNVs containing genes that participate in pathways previously implicated in ASD, such as the phosphoinositol signaling pathway (PIK3CA, GIRDIN), contactin-based networks of cell communication (CNTN6), and microcephalin (MCPH1) were found not to co-segregate with ASD phenotypes. In one family, a loss of CNTN5 co-segregated with disease. This indicates that most CNVs may by themselves not be sufficient to cause ASD, but still may contribute to the phenotype by additive or epistatic interactions with inherited (transmitted) mutations or non-genetic factors. Our study extends the scope of genome-wide CNV profiling beyond de novo CNVs in sporadic patients and may aid in uncovering missing heritability in genome-wide screening studies of complex psychiatric disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtorno Autístico
/
Variações do Número de Cópias de DNA
/
Testes Neuropsicológicos
Tipo de estudo:
Prognostic_studies
Limite:
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Neurogenetics
Assunto da revista:
GENETICA
/
NEUROLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Holanda