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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling by array of human clonal primary fibroblasts from patients with CDKL5 mutations

ABSTRACT: Mutations in the human CDKL5 gene have been shown to cause infantile spasms, as well as Rett syndrome-like phenotype. Because CDKL5 is subjected to X chromosome inactivation (XCI), individual cells from CDKL5 mutation girls either express the wild-type or mutant allele, likely resulting in different consequences at both the cellular and molecular levels. To identify these consequences, we carried out gene expression profiling on clonal populations derived from primary cultures of three patientsM-^R fibroblasts expressing either allele. A total of 16 up-regulated and 20 down-regulated genes were identified. The differentially expressed gene products, mostly involved in differentiation and oxidative stress may be related to a mechanism underlying mental retardation and epilepsy. Among these differentially expressed proteins, the apoptosis signal-regulated kinase MAP3K5 expression was found to be altered in non-neuronal, but also in neuronal CDKL5 deficient cells. Due to the fact that MAP3K5 activates MAP kinase pathway, which mediates signals leading to both differentiation and survival in neuronal cells, we suggest that a CDKL5 deficit may induce changes in synaptic plasticity in patientM-^Rs brain.

ORGANISM(S): Homo sapiens

SUBMITTER: Nicolas Cagnard

PROVIDER: E-MEXP-2833 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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