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RNA sequencing of creatine transporter (SLC6A8) deficient fibroblasts reveals impairment of the extracellular matrix.
- Source :
-
Human mutation [Hum Mutat] 2014 Sep; Vol. 35 (9), pp. 1128-35. Date of Electronic Publication: 2014 Jul 15. - Publication Year :
- 2014
-
Abstract
- Creatine transporter (SLC6A8) deficiency is the most common cause of cerebral creatine syndromes, and is characterized by depletion of creatine in the brain. Manifestations of this X-linked disorder include intellectual disability, speech/language impairment, behavior abnormalities, and seizures. At the moment, no effective treatment is available. In order to investigate the molecular pathophysiology of this disorder, we performed RNA sequencing on fibroblasts derived from patients. The transcriptomes of fibroblast cells from eight unrelated individuals with SLC6A8 deficiency and three wild-type controls were sequenced. SLC6A8 mutations with different effects on the protein product resulted in different gene expression profiles. Differential gene expression analysis followed by gene ontology term enrichment analysis revealed that especially the expression of genes encoding components of the extracellular matrix and cytoskeleton are altered in SLC6A8 deficiency, such as collagens, keratins, integrins, and cadherins. This suggests an important novel role for creatine in the structural development and maintenance of cells. It is likely that the (extracellular) structure of brain cells is also impaired in SLC6A8-deficient patients, and future studies are necessary to confirm this and to reveal the true functions of creatine in the brain.<br /> (© 2014 WILEY PERIODICALS, INC.)
- Subjects :
- Cell Line
Creatine genetics
Creatine metabolism
Gene Expression Profiling
Gene Expression Regulation
Humans
Male
Mutation
Plasma Membrane Neurotransmitter Transport Proteins genetics
Plasma Membrane Neurotransmitter Transport Proteins metabolism
Sequence Analysis, RNA
Synapses genetics
Synapses metabolism
Brain Diseases, Metabolic, Inborn genetics
Brain Diseases, Metabolic, Inborn metabolism
Creatine deficiency
Extracellular Matrix metabolism
Fibroblasts metabolism
Membrane Transport Proteins genetics
Mental Retardation, X-Linked genetics
Mental Retardation, X-Linked metabolism
Plasma Membrane Neurotransmitter Transport Proteins deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1004
- Volume :
- 35
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Human mutation
- Publication Type :
- Academic Journal
- Accession number :
- 24962355
- Full Text :
- https://doi.org/10.1002/humu.22609