The Genetic Landscape of Complex Childhood‐Onset Hyperkinetic Movement Disorders

Pérez‐Dueñas, Belén; Gorman, Kathleen; Marcé‐Grau, Anna; Ortigoza‐Escobar, Juan Darío; Macaya, Alfons; Danti, Federica Rachele; Barwick, Katy; Papandreou, Apostolos; Ng, Joanne; Meyer, Esther; Mohammad, Shekeeb S.; Smith, Martin A.; Muntoni, F.; Munot, Pinki; Uusimaa, Johanna; Vieira, Päivi; Sheridan, Eammon; Guerrini, Renzo; Cobben, Jan Maarten; Yılmaz, Sanem; Grandis, Elisa De; Dale, Russell C.; Pons, Roser; Peall, Kathryn J.; Leuzzi, Vincenzo; Kurian, Manju A.

doi:10.1002/mds.29182

Cited by 14 publications

(9 citation statements)

References 37 publications

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“…Importantly, glucose transport and glycogen synthesis preferred to select ADCY5 -mediated insulin-glucose pattern in LDM [ 53 ]. Glycogen storage was essential for myofiber movement [ 54 ], and the deletion of ADCY5 was related to abnormal muscle activity during active movement as neurotransmitter disorders caused by glucose transporter deficiency [ 55 ]. In this study, upregulated ( p < 0.05) ADCY5 expression was positively correlated with the weight of LEA (Fig.…”

Section: Discussionmentioning

confidence: 99%

Diverse WGBS profiles of longissimus dorsi muscle in Hainan black goats and hybrid goats

Ren,

Chen,

Zheng

et al. 2023

BMC Genom Data

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Background Goat products have played a crucial role in meeting the dietary demands of people since the Neolithic era, giving rise to a multitude of goat breeds globally with varying characteristics and meat qualities. The primary objective of this study is to pinpoint the pivotal genes and their functions responsible for regulating muscle fiber growth in the longissimus dorsi muscle (LDM) through DNA methylation modifications in Hainan black goats and hybrid goats. Methods Whole-genome bisulfite sequencing (WGBS) was employed to scrutinize the impact of methylation on LDM growth. This was accomplished by comparing methylation differences, gene expression, and their associations with growth-related traits. Results In this study, we identified a total of 3,269 genes from differentially methylated regions (DMR), and detected 189 differentially expressed genes (DEGs) through RNA-seq analysis. Hypo DMR genes were primarily enriched in KEGG terms associated with muscle development, such as MAPK and PI3K-Akt signaling pathways. We selected 11 hub genes from the network that intersected the gene sets within DMR and DEGs, and nine genes exhibited significant correlation with one or more of the three LDM growth traits, namely area, height, and weight of loin eye muscle. Particularly, PRKG1 demonstrated a negative correlation with all three traits. The top five most crucial genes played vital roles in muscle fiber growth: FOXO3 safeguarded the myofiber’s immune environment, FOXO6 was involved in myotube development and differentiation, and PRKG1 facilitated vasodilatation to release more glucose. This, in turn, accelerated the transfer of glucose from blood vessels to myofibers, regulated by ADCY5 and AKT2, ultimately ensuring glycogen storage and energy provision in muscle fibers. Conclusion This study delved into the diverse methylation modifications affecting critical genes, which collectively contribute to the maintenance of glycogen storage around myofibers, ultimately supporting muscle fiber growth.

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Section: Discussionmentioning

confidence: 99%

Diverse WGBS profiles of longissimus dorsi muscle in Hainan black goats and hybrid goats

Ren,

Chen,

Zheng

et al. 2023

BMC Genom Data

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“…Hyperkinetic disorders encompass a spectrum of neurological conditions characterized by excessive, involuntary movements impacting various aspects of an individual's life [87]. One of the hallmark symptoms of hyperkinetic disorders is tremors, which are rhythmic, involuntary movements that can occur at rest or during voluntary actions.…”

Section: Signs and Symptoms Of Hyperkinetic Disordersmentioning

confidence: 99%

Advances in Understanding and Managing Movement Disorders: A Comprehensive Review

R. Santos

2024

Preprint

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Movement disorders encompass a diverse group of neurological conditions characterized by abnormal voluntary or involuntary movements. These disorders can be classified broadly into hyperkinetic and hypokinetic disorders. Excessive, involuntary movements, including tremors, dystonia, chorea, and myoclonus characterize hyperkinetic disorders. Tremors are rhythmic, involuntary movements occurring at rest or during movement. Dystonia involves sustained muscle contractions, leading to twisting and repetitive movements or abnormal postures. Chorea manifests as brief, irregular, involuntary movements that flow from one body part to another. Myoclonus consists of sudden, brief muscle contractions, either spontaneous or in response to a stimulus. Hypokinetic disorders are characterized by a lack of movement or difficulty initiating movement, as seen in Parkinson's disease and Parkinsonism. Parkinson's disease is a progressive neurological disorder that primarily affects movement, causing tremors, stiffness, and difficulty with balance and coordination. Parkinsonism refers to a group of disorders with similar symptoms to Parkinson's disease but with different underlying causes. Diagnosing movement disorders involves a thorough clinical evaluation, including a detailed medical history and physical examination. Neuroimaging studies such as MRI, CT scans, and functional imaging techniques may be used to assess brain structure and function. Additionally, laboratory tests, including genetic testing and biochemical markers, can help diagnose certain movement disorders.

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“…ADCY5-RMD is characterized by a variable combination of hyperkinetic movements, most commonly focal or generalized chorea, dystonia and myoclonus. [19][20][21][22][23][24][25] (Supplementary Table S4)…”

Section: Adcy5-rmd Clinical Features and Phenomenologymentioning

confidence: 99%

“…ADCY5‐RMD is characterized by a variable combination of hyperkinetic movements, most commonly focal or generalized chorea, dystonia and myoclonus. 19 , 20 , 21 , 22 , 23 , 24 , 25 (Supplementary Table S4 ) There is a predilection of the myoclonus and chorea for facial muscles (perioral and periorbital). 1 , 2 , 26 …”

Section: Adcy5‐rmdmentioning

confidence: 99%

Scoping Review onADCY5‐Related Movement Disorders

Menon,

Nilles,

Silveira‐Moriyama

et al. 2023

Movement Disord Clin Pract

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Background Adenylyl cyclase 5 (ADCY5)‐related movement disorder (ADCY5‐RMD) is a rare, childhood‐onset disease resulting from pathogenic variants in the ADCY5 gene. The clinical features, diagnostic options, natural history, and treatments for this disease are poorly characterized and have never been established through a structured approach. Objective This scoping review attempts to summarize all available clinical literature on ADCY5‐RMD. Methods Eighty‐seven articles were selected for inclusion in this scoping review. The majority of articles identified were case reports or case series. Results These articles demonstrate that patients with ADCY5‐RMD suffer from permanent and/ or paroxysmal hyperkinetic movements. The paroxysmal episodes can be worsened by environmental triggers, in particular the sleep–wake transition phase in the early morning. Occurrence of nocturnal paroxysmal dyskinesias and perioral twitches are highly suggestive of the diagnosis when present. In the majority of patients intellectual capacity is preserved. ADCY5‐RMD is considered a non‐progressive disorder, with inter‐individual variations in evolution with aging. Somatic mosaicism, mode of inheritance and the location of the mutation within the protein can influence phenotype. Conclusions The current evidence for therapeutic options for ADCY5‐RMD is limited: caffeine, benzodiazepines and deep brain stimulation have been consistently reported to be useful in case reports and case series.

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The Genetic Landscape of Complex Childhood‐Onset Hyperkinetic Movement Disorders

Cited by 14 publications

References 37 publications

Diverse WGBS profiles of longissimus dorsi muscle in Hainan black goats and hybrid goats

Diverse WGBS profiles of longissimus dorsi muscle in Hainan black goats and hybrid goats

Advances in Understanding and Managing Movement Disorders: A Comprehensive Review

Scoping Review onADCY5‐Related Movement Disorders

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