Loss of the scavenger mRNA decapping enzyme DCPS causes syndromic intellectual disability with neuromuscular defects.
Hum Mol Genet
; 24(11): 3163-71, 2015 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-25712129
ABSTRACT
mRNA decay is an essential and active process that allows cells to continuously adapt gene expression to internal and environmental cues. There are two mRNA degradation pathways 3' to 5' and 5' to 3'. The DCPS protein is the scavenger mRNA decapping enzyme which functions in the last step of the 3' end mRNA decay pathway. We have identified a DCPS pathogenic mutation in a large family with three affected individuals presenting with a novel recessive syndrome consisting of craniofacial anomalies, intellectual disability and neuromuscular defects. Using patient's primary cells, we show that this homozygous splice mutation results in a DCPS loss-of-function allele. Diagnostic biochemical analyses using various m7G cap derivatives as substrates reveal no DCPS enzymatic activity in patient's cells. Our results implicate DCPS and more generally RNA catabolism, as a critical cellular process for neurological development, normal cognition and organismal homeostasis in humans.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anormalidades Múltiplas
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Endorribonucleases
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Deficiência Intelectual
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Hipotonia Muscular
Tipo de estudo:
Etiology_studies
Limite:
Child
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Child, preschool
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Humans
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Male
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Singapura