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

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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 variousm7G 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.
Original languageEnglish (US)
Pages (from-to)3163-3171
Number of pages9
JournalHuman Molecular Genetics
Volume24
Issue number11
DOIs
StatePublished - Dec 15 2014
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-02-15

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Genetics(clinical)

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