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

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

  • Hum Mol Genet. 2015 Jun 1;24(11):3163-71. doi: 10.1093/hmg/ddv067.
Calista K L Ng 1,  Mohammad Shboul 1,  Valerio Taverniti 2,  Carine Bonnard 1,  Hane Lee 3,  Ascia Eskin 4,  Stanley F Nelson 5,  Mohammed Al-Raqad 6,  Samah Altawalbeh 6,  Bertrand Séraphin 7,  Bruno Reversade 8
Affiliations

Affiliations

  • 1 Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Singapore 138648, Singapore.
  • 2 IGBMC, CNRS UMR 1704/INSERM U964/Université de Strasbourg, Illkirch, France.
  • 3 Department of Pathology and Laboratory Medicine.
  • 4 Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • 5 Department of Pathology and Laboratory Medicine Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • 6 Queen Rania Paediatric Hospital, King Hussein Medical Centre, Royal Medical Services, Amman, Jordan.
  • 7 IGBMC, CNRS UMR 1704/INSERM U964/Université de Strasbourg, Illkirch, France bertrand.seraphin@igbmc.fr bruno@reversade.com.
  • 8 Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Singapore 138648, Singapore Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore bertrand.seraphin@igbmc.fr bruno@reversade.com.
PMID: 25712129 DOI: 10.1093/hmg/ddv067
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.

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