Abstract
P80 - Connection between glucose metabolism and gene expression of critical
neuromuscular components in Pompe's disease: new hints explainig the
hypotonic phenotye?
Laura DT Vo Ngoc1, Randy Osei1, Katrin Dohr2, Karen Sermon3, Sara Seneca1 & Alexander Gheldof1
1 Center of Medical Genetics, UZBrussel
2 Department of Paediatrics and Adolescent Medicine Graz, Austria
3 Reproduction and Genetics Unit, Vrije Universiteit Brussel (VUB)
Pompe's disease is caused by the presence of bi-allelic pathogenic alterations in the GAA gene,
resulting in the inability of patients to degrade glycogen. This translates to a hypotonic phenotype in
combination with hypertrophic cardiomyopathy in severe cases. We performed genome wide
mRNAseq on fibroblasts of Pompe patients and observed a marked increase of the transcription
factor PPARgamma, together with an mRNA decrease of the neuromuscular junction component
COL13A1 and the neuronally expressed KCNMA1 potassium ion channel. We have treated patients
fibroblasts with the PPARgamma inhibitor G3335 and could observe a significant upregulation of both
COL13A1 and KCNMA1 mRNA, indicating that PPARgamma functionality indeed impacts on
expression of both genes. However, we could only show this effect in a subset of patients. As
PPARgamma is a known important regulator of the energy metabolism and glucose is the buidling
block of glycogen, we speculated that altering the glucose content of the culture medium could
potentially impact on the expression of COL13A1 and KCNMA1 as well. Growing Pompe fibroblasts in
glucose free medium indeed resulted in a significant mRNA upregulation of COL13A1 and KCNMA1
mRNA respectively. This is a important new finding which directly links the cellular glucose
metabolism or uptake to the expression of two important mediators of neuromuscular junction and
neuronal functionality. Furthermore, this finding could imply that a treatment regime of Pompe patients
with a glucose restricted diet could be beneficial.
Original language | English |
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Publication status | Unpublished - Feb 2022 |
Event | 22nd annual joint meeting BeSHG & NVHG: genetics retreat - Duration: 20 Apr 2022 → 22 Apr 2022 https://beshg.be/index.php/meeting |
Conference
Conference | 22nd annual joint meeting BeSHG & NVHG |
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Period | 20/04/22 → 22/04/22 |
Internet address |