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RNA Sequencing of Creatine Transporter ( SLC 6 A 8) Deficient Fibroblasts Reveals Impairment of the Extracellular Matrix
Author(s) -
Nota Benjamin,
Ndika Joseph D. T.,
Kamp Jiddeke M.,
Kanhai Warsha A.,
Dooren Silvy J. M.,
Wiel Mark A.,
Pals Gerard,
Salomons Gajja S.
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22609
Subject(s) - biology , transcriptome , gene , creatine , gene expression , genetics , extracellular matrix , microbiology and biotechnology , endocrinology , medicine
ABSTRACT Creatine transporter ( SLC 6 A 8) 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 SLC 6 A 8 deficiency and three wild‐type controls were sequenced. SLC 6 A 8 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 SLC 6 A 8 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 SLC 6 A 8‐deficient patients, and future studies are necessary to confirm this and to reveal the true functions of creatine in the brain.

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