title: Loss of the scavenger mRNA decapping enzyme DCPS causes syndromic intellectual disability with neuromuscular defects.
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.
authors.affiliation: Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Singapore 138648, Singapore.
authors.forename: Calista K L
authors.initials: CK
authors.lastname: Ng
authors.affiliation: Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Singapore 138648, Singapore.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shboul
authors.affiliation: IGBMC, CNRS UMR 1704/INSERM U964/Université de Strasbourg, Illkirch, France.
authors.forename: Valerio
authors.initials: V
authors.lastname: Taverniti
authors.affiliation: Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Singapore 138648, Singapore.
authors.forename: Carine
authors.initials: C
authors.lastname: Bonnard
authors.affiliation: Department of Pathology and Laboratory Medicine.
authors.forename: Hane
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Ascia
authors.initials: A
authors.lastname: Eskin
authors.affiliation: Department of Pathology and Laboratory Medicine Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Nelson
authors.affiliation: Queen Rania Paediatric Hospital, King Hussein Medical Centre, Royal Medical Services, Amman, Jordan.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Raqad
authors.affiliation: Queen Rania Paediatric Hospital, King Hussein Medical Centre, Royal Medical Services, Amman, Jordan.
authors.forename: Samah
authors.initials: S
authors.lastname: Altawalbeh
authors.affiliation: IGBMC, CNRS UMR 1704/INSERM U964/Université de Strasbourg, Illkirch, France bertrand.seraphin@igbmc.fr bruno@reversade.com.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Séraphin
authors.affiliation: 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.
authors.forename: Bruno
authors.initials: B
authors.lastname: Reversade
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004722:Endoribonucleases / Q000172:deficiency / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009123:Muscle Hypotonia / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites; D013577:Syndrome
chemical_list: D022821:RNA Splice Sites; D004722:Endoribonucleases; C485332:DcpS protein, human