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SHR Neuro Krebs Kardio Lipid

Windpassinger, C; Piard, J; Bonnard, C; Alfadhel, M; Lim, S; Bisteau, X; Blouin, S; Ali, NB; Ng, AYJ; Lu, H; Tohari, S; Talib, SZA; van Hul, N; Caldez, MJ; Van Maldergem, L; Yigit, G; Kayserili, H; Youssef, SA; Coppola, V; de Bruin, A; Tessarollo, L; Choi, H; Rupp, V; Roetzer, K; Roschger, P; Klaushofer, K; Altmüller, J; Roy, S; Venkatesh, B; Ganger, R; Grill, F; Ben Chehida, F; Wollnik, B; Altunoglu, U; Al Kaissi, A; Reversade, B; Kaldis, P.
CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays.
Am J Hum Genet. 2017; 101(3):391-403 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Rupp Verena
Windpassinger Christian

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Plum Analytics:
Number of Figures: 3
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In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth. To validate and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mice. Homozygous Cdk10-knockout mice died postnatally with severe growth retardation, skeletal defects, and kidney and lung abnormalities, symptoms that partly resemble the disease's effect in humans. Fibroblasts derived from affected individuals and Cdk10-knockout mouse embryonic fibroblasts (MEFs) proliferated normally; however, Cdk10-knockout MEFs developed longer cilia. Comparative transcriptomic analysis of mutant and wild-type mouse organs revealed lipid metabolic changes consistent with growth impairment and altered ciliogenesis in the absence of CDK10. Our results document the CDK10 loss-of-function phenotype and point to a function for CDK10 in transducing signals received at the primary cilia to sustain embryonic and postnatal development. Copyright © 2017 American Society of Human Genetics. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Cell Cycle -
Cell Proliferation -
Cells, Cultured -
Child -
Child, Preschool -
Cilia - metabolism
Cilia - pathology
Cyclin-Dependent Kinases - genetics
Cyclin-Dependent Kinases - physiology
Developmental Disabilities - genetics
Developmental Disabilities - pathology
Embryo, Mammalian - metabolism
Embryo, Mammalian - pathology
Female -
Fibroblasts - metabolism
Fibroblasts - pathology
Growth Disorders - genetics
Growth Disorders - pathology
Humans -
Infant -
Male -
Mice -
Mice, Knockout -
Mutation -
Pedigree -
Phosphorylation -
Signal Transduction -
Spine - abnormalities
Spine - metabolism
Spine - pathology

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