Human Molecular Genetics 2015-06-01

Loss of the scavenger mRNA decapping enzyme DCPS causes syndromic intellectual disability with neuromuscular defects.

Calista K L Ng, Mohammad Shboul, Valerio Taverniti, Carine Bonnard, Hane Lee, Ascia Eskin, Stanley F Nelson, Mohammed Al-Raqad, Samah Altawalbeh, Bertrand Séraphin, Bruno Reversade

文献索引：Hum. Mol. Genet. 24(11) , 3163-71, (2015)

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摘要

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. © The Author 2015. Published by Oxford University Press.