Intellectual disability associated with a homozygous missense mutation in THOC6.
Orphanet J Rare Dis
; 8: 62, 2013 Apr 26.
Article
em En
| MEDLINE
| ID: mdl-23621916
ABSTRACT
BACKGROUND:
We recently described a novel autosomal recessive neurodevelopmental disorder with intellectual disability in four patients from two related Hutterite families. Identity-by-descent mapping localized the gene to a 5.1 Mb region at chromosome 16p13.3 containing more than 170 known or predicted genes. The objective of this study was to identify the causative gene for this rare disorder. METHODS ANDRESULTS:
Candidate gene sequencing followed by exome sequencing identified a homozygous missense mutation p.Gly46Arg, in THOC6. No other potentially causative coding variants were present within the critical region on chromosome 16. THOC6 is a member of the THO/TREX complex which is involved in coordinating mRNA processing with mRNA export from the nucleus. In situ hybridization showed that thoc6 is highly expressed in the midbrain and eyes. Cellular localization studies demonstrated that wild-type THOC6 is present within the nucleus as is the case for other THO complex proteins. However, mutant THOC6 was predominantly localized to the cytoplasm, suggesting that the mutant protein is unable to carry out its normal function. siRNA knockdown of THOC6 revealed increased apoptosis in cultured cells.CONCLUSION:
Our findings associate a missense mutation in THOC6 with intellectual disability, suggesting the THO/TREX complex plays an important role in neurodevelopment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Mutação de Sentido Incorreto
/
Deficiência Intelectual
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Orphanet J Rare Dis
Assunto da revista:
MEDICINA
Ano de publicação:
2013
Tipo de documento:
Article