Identification of candidate genes involved in the etiology of sporadic Tourette syndrome by exome sequencing.
Am J Med Genet B Neuropsychiatr Genet
; 174(7): 712-723, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28608572
ABSTRACT
Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by chronic motor and vocal tics. Although there is a large genetic contribution, the genetic architecture of TS remains unclear. Exome sequencing has successfully revealed the contribution of de novo mutations in sporadic cases with neuropsychiatric disorders such as autism and schizophrenia. Here, using exome sequencing, we investigated de novo mutations in individuals with sporadic TS to identify novel risk loci and elucidate the genetic background of TS. Exome analysis was conducted for sporadic TS cases nine trio families and one quartet family with concordant twins were investigated. Missense mutations were evaluated using functional prediction algorithms, and their population frequencies were calculated based on three public databases. Gene expression patterns in the brain were analyzed using the BrainSpan Developmental Transcriptome. Thirty de novo mutations, including four synonymous and four missense mutations, were identified. Among the missense mutations, one in the rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR)-coding gene (rs140964083 G > A, found in one proband) was predicted to be hazardous. In the three public databases analyzed, variants in the same SNP locus were absent, and variants in the same gene were either absent or present at an extremely low frequency (3/5,008), indicating the rarity of hazardous RICTOR mutations in the general population. The de novo variant of RICTOR may be implicated in the development of sporadic TS, and RICTOR is a novel candidate factor for TS etiology.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Tourette
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Análise de Sequência de DNA
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Mutação de Sentido Incorreto
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Exoma
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Proteína Companheira de mTOR Insensível à Rapamicina
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Med Genet B Neuropsychiatr Genet
Assunto da revista:
GENETICA MEDICA
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NEUROLOGIA
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PSIQUIATRIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão