Diff: MEGF10
Comparing revision #1 (2023-06-09 23:56:11) with revision #2 (2026-06-22 10:20:41).
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'''MEGF10''' is a human protein-coding gene whose name stands for '''multiple EGF-like domains 10'''. It is located on chromosome 5 at 5q23.2 and is associated with MEGF10-related myopathy, including [[EMARDD]]. |
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MEGF10 (Multiple Epidermal Growth Factor-Like Domains 10) is a gene located on chromosome 3p25.3. It encodes a transmembrane protein that plays a crucial role in muscle development and function. Mutations in the MEGF10 gene have been associated with a rare genetic disorder known as early-onset myopathy, areflexia, respiratory distress, and dysphagia ([[EMARDD]]). |
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Older wording on some imported pages placed MEGF10 on chromosome 3p25.3. That is not correct. Current NCBI records place MEGF10 on chromosome 5q23.2. |
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== Gene Structure and Protein == |
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The MEGF10 gene spans approximately 126 kilobases on the genomic DNA and consists of 27 exons. Alternative splicing of the MEGF10 mRNA produces multiple isoforms of the protein. The MEGF10 protein is a type I transmembrane protein that contains multiple epidermal growth factor-like (EGF-like) domains, which are involved in protein-protein interactions. |
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== Gene and Protein == |
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MEGF10 encodes a transmembrane protein with multiple epidermal growth factor-like domains. These domains are involved in protein interactions and are part of the reason the protein is grouped with other EGF-domain-containing proteins. |
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== Function and Mechanism == |
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MEGF10 is primarily expressed in skeletal muscle during embryonic development and plays a crucial role in myogenesis (muscle formation) and muscle maintenance. The protein is involved in the fusion of myoblasts, which are precursor cells that differentiate into muscle fibers. MEGF10 promotes myoblast fusion by interacting with other proteins involved in this process, such as myomaker and myomerger. |
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NCBI's Genetic Testing Registry lists MEGF10 as a protein-coding gene on chromosome 5, with 31 exons in the current reference record. The gene has several transcript isoforms. |
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Additionally, MEGF10 is involved in the development and maintenance of neuromuscular junctions (NMJs), which are specialized synapses between motor neurons and muscle fibers. It promotes the clustering of acetylcholine receptors at the NMJ and ensures proper communication between nerves and muscles. |
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== Biological Role == |
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MEGF10 is studied mainly for its role in muscle development and maintenance. Published work links the gene to satellite cell myogenesis, a process involving muscle precursor cells that helps build and repair skeletal muscle. |
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== Clinical Significance == |
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Mutations in the MEGF10 gene are associated with early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD). This rare genetic disorder is characterized by muscle weakness, areflexia (absence of reflexes), respiratory difficulties, and feeding problems due to dysphagia (difficulty swallowing). |
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The gene has also been studied in other biological contexts, including cell clearance and nervous-system biology, but its clearest clinical relevance on iWiki is its role in congenital muscle disease. |
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EMARDD typically manifests in infancy or early childhood, with affected individuals displaying generalized muscle weakness and delayed motor milestones. Respiratory distress can range from mild respiratory insufficiency to the need for mechanical ventilation. Dysphagia can lead to feeding difficulties and potential complications such as aspiration. |
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== MEGF10-Related Myopathy == |
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Biallelic pathogenic variants in MEGF10 can cause MEGF10-related myopathy. The best-known severe form is early-onset myopathy, areflexia, respiratory distress and dysphagia, usually shortened to [[EMARDD]]. |
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The exact mechanisms by which MEGF10 mutations lead to EMARDD are not yet fully understood. However, it is believed that these mutations impair the normal function of the MEGF10 protein, disrupting myoblast fusion, neuromuscular junction formation, and muscle development. |
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Typical features can include early muscle weakness, low muscle tone, absent or reduced reflexes, breathing difficulty, swallowing problems, scoliosis and delayed motor milestones. Severity varies. Some affected people need ventilatory support early in life, while milder presentations may progress more slowly. |
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== Diagnosis and Management == |
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Diagnosis of EMARDD is based on clinical evaluation, including physical examination, assessment of motor development, electromyography (EMG), and muscle biopsies. Genetic testing can confirm the presence of mutations in the MEGF10 gene. |
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The inheritance pattern is autosomal recessive. This means an affected person usually has pathogenic variants in both copies of MEGF10, with parents often being unaffected carriers. |
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Currently, there is no specific treatment for EMARDD. Management is focused on supportive care, addressing the individual symptoms and complications associated with the disorder. Physical therapy can help maintain muscle strength and mobility. Respiratory support, including assisted ventilation, may be necessary in severe cases. Feeding and swallowing difficulties may require interventions such as modified diets and feeding techniques. |
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== Diagnosis == |
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Diagnosis is based on clinical findings and genetic testing. A neuromuscular team may also use muscle biopsy, electromyography, respiratory assessment, swallowing assessment and imaging when building the diagnosis. |
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== Research and Future Perspectives == |
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Research on MEGF10 and its role in muscle development and function is ongoing. Further studies are needed to gain a deeper understanding of the molecular mechanisms underlying EMARDD and the specific interactions of MEGF10 with other proteins involved in myoblast fusion and neuromuscular junction formation. |
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Genetic testing can confirm MEGF10 involvement, but results need specialist interpretation. The clinical picture matters because many congenital myopathies can overlap in early symptoms. |
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Increased knowledge of MEGF10 function and its role in muscle biology may lead to the development of potential therapeutic strategies for individuals affected by EMARDD and related muscle disorders. |
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== Management == |
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There is no established cure for MEGF10-related myopathy. Care is supportive and usually multidisciplinary. |
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Management may include respiratory support, feeding and swallowing support, physiotherapy, occupational therapy, orthopaedic care for scoliosis or contractures, nutrition support and genetic counselling. |
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== Research == |
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Research on MEGF10 remains limited because the condition is rare. Case reports and small series have expanded the recognised range of MEGF10-related disease, including milder forms as well as severe infantile disease. |
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== See Also == |
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* [[EMARDD]] |
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* [[Congenital_Myopathy]] |
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* [[Neuromuscular_Disorders]] |
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== References == |
== References == |
* [https://www.ncbi.nlm.nih.gov/gtr/genes/84466/ NCBI Genetic Testing Registry: MEGF10] |
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* [https://panelapp.genomicsengland.co.uk/panels/225/gene/MEGF10/ Genomics England PanelApp: MEGF10] |
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* [https://rarediseases.info.nih.gov/diseases/12199/megf10-related-myopathy GARD: MEGF10-related myopathy] |
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* [https://pubmed.ncbi.nlm.nih.gov/22101682/ Logan et al.: Mutations in MEGF10 cause EMARDD] |
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* [https://pmc.ncbi.nlm.nih.gov/articles/PMC8620084/ Phenotypic variability of MEGF10 variants causing congenital myopathy] |
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# Logan CV, Lucke B, Pottinger C, et al. Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD). Nat Genet. 2011;43(12):1189-1192. doi:10.1038/ng.975. |
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# Rivas E, Zuñiga S, Töpf A, et al. A Founder Mutation in MEGF10 Causes a Mendelian Form of Congenital Myasthenic Syndrome with Dropped Head and Bulbar Weakness. Am J Hum Genet. 2016;99(4):849-857. doi:10.1016/j.ajhg.2016.07.016. |
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# Hicks D, Vogt J, Benton A, et al. Mutations in MEGF10 gene are a rare cause of autosomal recessive congenital myasthenic syndrome. Neurology. 2014;82(11):967-974. doi:10.1212/WNL.0000000000000216. |
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[[Category:Genetics]] |
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[[Category:Medicine]] |
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[[Category:Neuromuscular Disorders]] |