2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Mitochondrial Dysfunction in Rett Syndrome: Searching for Biomarkers

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This study investigates the potential of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) as biomarkers for Rett syndrome (RTT). RTT is a severe neurodevelopmental disorder caused by mutations in the MECP2 gene. Mitochondrial dysfunction and inflammation are observed in RTT patients. Currently, there are no effective treatments for RTT, and there is a need for biomarkers to predict disease severity and monitor treatment efficacy.<br /><br />The researchers analyzed FGF21 and GDF15 concentrations in serum samples from a mouse model of RTT and plasma samples from female RTT patients. They used quantitative enzyme-linked immunosorbent assays to measure the concentrations and analyzed the data statistically.<br /><br />The results show that FGF21 concentrations are significantly higher in female Mecp2-deficient mice compared to wild-type mice, but not in males. GDF15 concentrations appear to be higher in wild-type males compared to Mecp2-deficient males, and there is a trend towards increased concentrations in female Mecp2 mice compared to controls. However, these differences are not statistically significant.<br /><br />In the human cohort, median FGF21 and GDF15 levels in RTT patients are higher than in unaffected females, but these differences are not statistically significant. All RTT patients on sodium valproate therapy have elevated FGF21 and GDF15 levels. It is noted that larger cohorts and a multi-omic approach may be necessary to identify other potential biomarkers.<br /><br />Overall, this study suggests that FGF21 and GDF15 may not be suitable diagnostic markers for RTT. Further research with larger cohorts and additional biomarkers is needed to improve monitoring and treatment of RTT.

Asset Subtitle

Presenting Author - Ashley Hertzog, BSc; Co-Author - Adviye Ayper Tolun, PhD; Co-Author - Carolyn Ellaway, MBBS PHD; Co-Author - Wendy Gold, PhD; Co-Author - Gladys Ho, PhD;

Meta Tag

Biochemical genetics

Identification of Disease Genes

Mitochondria

Co-Author Adviye Ayper Tolun, PhD

Co-Author Carolyn Ellaway, MBBS PHD

Co-Author Wendy Gold, PhD

Co-Author Gladys Ho, PhD

Presenting Author Ashley Hertzog, BSc

Keywords

fibroblast growth factor 21

FGF21

growth differentiation factor 15

GDF15

Rett syndrome

MECP2 gene

mitochondrial dysfunction

inflammation

biomarkers

disease severity