FGF-21 as a Potential Biomarker for Mitochondrial Diseases

The diagnosis of mitochondrial diseases is still challenging due to clinical and genetical heterogeneity. The development of advanced technologies including Whole-Exome- Sequencing (WES) and Whole-Genome-Sequencing (WGS) has led to improvements in genetic diagnosis. However, a reliable biomarker in serum could enhance and ease the diagnosis and indeed reduce the need for muscle biopsy. Several studies suggest Fibroblast growth factor 21 (FGF-21) as a biomarker for diagnosis in mitochondrial disorders. It is known, that in patients with mitochondrial disorders, the expression of FGF-21 gets elevated in an effort to counteract the underlying metabolic deficiency. The growth and differentiation factor 15 (GDF-15) has been described as a potential biomarker for mitochondrial diseases, too. In the present review, a literature research, using PubMed database about the reliability of FGF-21 as a biomarker for mitochondrial disorders and its comparison with GDF-15 has been performed.

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Potential biomarker of fibroblast growth factor 21 in valproic acid‐treated livers

BioFactors ◽

10.1002/biof.1519 ◽

2019 ◽

Vol 45 (5) ◽

pp. 740-749 ◽

Cited By ~ 9

Author(s):

Xiaoxiao Xu ◽

Chao Guo ◽

Xiaoliu Liang ◽

Rong Li ◽

Jian Chen

Keyword(s):

Valproic Acid ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Potential Biomarker

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Advancing genomic approaches to the molecular diagnosis of mitochondrial disease

Essays in Biochemistry ◽

10.1042/ebc20170110 ◽

2018 ◽

Vol 62 (3) ◽

pp. 399-408 ◽

Cited By ~ 23

Author(s):

Sarah Louise Stenton ◽

Holger Prokisch

Keyword(s):

Molecular Diagnosis ◽

Mitochondrial Disease ◽

Genetic Diagnosis ◽

Mitochondrial Diseases ◽

Candidate Gene Approach ◽

Disease Genes ◽

Variant Interpretation ◽

Diagnostic Challenge ◽

Whole Exome ◽

Prior Analysis

Mitochondrial diseases present a diagnostic challenge due to their clinical and genetic heterogeneity. Achieving comprehensive molecular diagnosis via a conventional candidate-gene approach is likely, therefore, to be labour- and cost-intensive given the expanding number of mitochondrial disease genes. The advent of whole exome sequencing (WES) and whole genome sequencing (WGS) hold the potential of higher diagnostic yields due to the universality and unbiased nature of the methods. However, these approaches are subject to the escalating challenge of variant interpretation. Thus, integration of functional ‘multi-omics’ data, such as transcriptomics, is emerging as a powerful complementary tool in the diagnosis of mitochondrial disease patients for whom extensive prior analysis of DNA sequencing has failed to return a genetic diagnosis.

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Fibroblast Growth Factor 21 as a Potential Biomarker for Improved Locomotion and Olfaction Detection Ability after Weight Reduction in Obese Mice

Nutrients ◽

10.3390/nu13092916 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2916

Author(s):

Nicole Power Guerra ◽

Alisha Parveen ◽

Daniel Bühler ◽

David Leon Brauer ◽

Luisa Müller ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Weight Reduction ◽

Treadmill Exercise ◽

Dietary Change ◽

Fibroblast Growth Factor 21 ◽

Restricted Feeding ◽

Fibroblast Growth ◽

Obese Mice ◽

Potential Biomarker

Obesity is one of the most challenging diseases of the 21st century and is accompanied by behavioural disorders. Exercise, dietary adjustments, or time-restricted feeding are the only successful long-term treatments to date. Fibroblast growth factor 21 (FGF21) plays a key role in dietary regulation, but FGF21 resistance is prevalent in obesity. The aim of this study was to investigate in obese mice whether weight reduction leads to improved behaviour and whether these behavioural changes are associated with decreased plasma FGF21 levels. After establishing a model for diet-induced obesity, mice were subjected to three different interventions for weight reduction, namely dietary change, treadmill exercise, or time-restricted feeding. In this study, we demonstrated that only the combination of dietary change and treadmill exercise affected all parameters leading to a reduction in weight, fat, and FGF21, as well as less anxious behaviour, higher overall activity, and improved olfactory detection abilities. To investigate the interrelationship between FGF21 and behavioural parameters, feature selection algorithms were applied designating FGF21 and body weight as one of five highly weighted features. In conclusion, we concluded from the complementary methods that FGF21 can be considered as a potential biomarker for improved behaviour in obese mice after weight reduction.

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Delineation of molecular findings by whole exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population

10.21203/rs.3.rs-23585/v2 ◽

2020 ◽

Author(s):

Mandy Ho-Yin Tsang ◽

Anna Ka-Yee Kwong ◽

Kate Lok-San Chan ◽

Jasmine Lee-Fong Fung ◽

Mullin Ho-Chung Yu ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Chinese Population ◽

Founder Mutation ◽

Diagnostic Yield ◽

Genetic Diagnosis ◽

Mitochondrial Diseases ◽

Chinese Patients ◽

Southern Chinese ◽

Whole Exome

Abstract BackgroundMitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs.MethodsWe recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines.ResultsSixty-six patients with pre-biopsy MDC scores of 3–8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n=3, two were siblings), ALDH5A1 , ARX , FA2H , KCNT1 , LDHD , NEFL , NKX2-2 , TBCK , and WAC.ConclusionsWe confirmed that the COQ4 :c.370G>A, p.(Gly124Ser) variant was a recurrent founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous.

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Delineation of molecular findings by whole exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population

10.21203/rs.3.rs-23585/v1 ◽

2020 ◽

Author(s):

Mandy Ho-Yin Tsang ◽

Anna Ka-Yee Kwong ◽

Kate Lok-San Chan ◽

Jasmine Lee-Fong Fung ◽

Mullin Ho-Chung Yu ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Chinese Population ◽

Founder Mutation ◽

Diagnostic Yield ◽

Genetic Diagnosis ◽

Mitochondrial Diseases ◽

Chinese Patients ◽

Southern Chinese ◽

Whole Exome

Abstract Background Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs.Methods We recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines.Results Sixty-six patients with pre-biopsy MDC scores of 3–8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n=3, two were siblings), ALDH5A1, ARX, FA2H, KCNT1, LDHD, NEFL, NKX2-2, TBCK, and WAC.Conclusions We confirmed that the COQ4:c.370G>A, p.(Gly124Ser) variant was a recurrent founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous.

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Delineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population

Human Genomics ◽

10.1186/s40246-020-00278-0 ◽

2020 ◽

Vol 14 (1) ◽

Author(s):

Mandy H.Y. Tsang ◽

Anna K.Y. Kwong ◽

Kate L.S. Chan ◽

Jasmine L.F. Fung ◽

Mullin H.C. Yu ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Chinese Population ◽

Founder Mutation ◽

Diagnostic Yield ◽

Genetic Diagnosis ◽

Mitochondrial Diseases ◽

Chinese Patients ◽

Southern Chinese ◽

Whole Exome

Abstract Background Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs. Methods We recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤ 1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines. Results Sixty-six patients with pre-biopsy MDC scores of 3–8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n = 3, two were siblings), ALDH5A1, ARX, FA2H, KCNT1, LDHD, NEFL, NKX2-2, TBCK, and WAC. Conclusions We confirmed that the COQ4:c.370G>A, p.(Gly124Ser) variant, was a founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous.

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