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• W3021137551 abstract "Abstract Background Distal motor neuropathies with a genetic origin have a heterogeneous clinical presentation with overlapping features affecting distal nerves and including spinal muscular atrophies and amyotrophic lateral sclerosis. This indicates that their genetic background is heterogeneous. Patient and methods In this work, we have identified and characterized the genetic and molecular base of a patient with a distal sensorimotor neuropathy of unknown origin. For this study, we performed whole‐exome sequencing, molecular modelling, cloning and expression of mutant gene, and biochemical and cell biology analysis of the mutant protein. Results A novel homozygous recessive mutation in the human VRK1 gene, coding for a chromatin kinase, causing a substitution (c.637T > C; p.Tyr213His) in exon 8, was detected in a patient presenting since childhood a progressive distal sensorimotor neuropathy and spinal muscular atrophy syndrome, with normal intellectual development. Molecular modelling predicted this mutant VRK1 has altered the kinase activation loop by disrupting its interaction with the C‐terminal regulatory region. The p.Y213H mutant protein has a reduced kinase activity with different substrates, including histones H3 and H2AX, proteins involved in DNA damage responses, such as p53 and 53BP1, and coilin, the scaffold for Cajal bodies. The mutant VRK1(Y213H) protein is unable to rescue the formation of Cajal bodies assembled on coilin, in the absence of wild‐type VRK1. Conclusion The VRK1(Y213H) mutant protein alters the activation loop, impairs the kinase activity of VRK1 causing a functional insufficiency that impairs the formation of Cajal bodies assembled on coilin, a protein that regulates SMN1 and Cajal body formation." @default.
• W3021137551 created "2020-05-13" @default.
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• W3021137551 date "2020-05-01" @default.
• W3021137551 modified "2023-10-02" @default.
• W3021137551 title "VRK1 (Y213H) homozygous mutant impairs Cajal bodies in a hereditary case of distal motor neuropathy" @default.
• W3021137551 cites W1023090330 @default.
• W3021137551 cites W1518966340 @default.
• W3021137551 cites W1973312149 @default.
• W3021137551 cites W1974432810 @default.
• W3021137551 cites W1976144441 @default.
• W3021137551 cites W1991772727 @default.
• W3021137551 cites W1991794140 @default.
• W3021137551 cites W1996016488 @default.
• W3021137551 cites W1999598905 @default.
• W3021137551 cites W2002197824 @default.
• W3021137551 cites W2007962137 @default.
• W3021137551 cites W2022040474 @default.
• W3021137551 cites W2024907326 @default.
• W3021137551 cites W2027773741 @default.
• W3021137551 cites W2032174132 @default.
• W3021137551 cites W2038462501 @default.
• W3021137551 cites W2042917585 @default.
• W3021137551 cites W2043348864 @default.
• W3021137551 cites W2044585191 @default.
• W3021137551 cites W2047970730 @default.
• W3021137551 cites W2051978340 @default.
• W3021137551 cites W2059145105 @default.
• W3021137551 cites W2059642730 @default.
• W3021137551 cites W2071515332 @default.
• W3021137551 cites W2082765455 @default.
• W3021137551 cites W2082841497 @default.
• W3021137551 cites W2083146650 @default.
• W3021137551 cites W2097097435 @default.
• W3021137551 cites W2098746581 @default.
• W3021137551 cites W2102554713 @default.
• W3021137551 cites W2104746705 @default.
• W3021137551 cites W2106830069 @default.
• W3021137551 cites W2112217896 @default.
• W3021137551 cites W2113768195 @default.
• W3021137551 cites W2121134287 @default.
• W3021137551 cites W2126848848 @default.
• W3021137551 cites W2127411865 @default.
• W3021137551 cites W2133017629 @default.
• W3021137551 cites W2138482402 @default.
• W3021137551 cites W2143079500 @default.
• W3021137551 cites W2157303903 @default.
• W3021137551 cites W2160265494 @default.
• W3021137551 cites W2166437336 @default.
• W3021137551 cites W2333607779 @default.
• W3021137551 cites W2408006679 @default.
• W3021137551 cites W2418084578 @default.
• W3021137551 cites W2438918770 @default.
• W3021137551 cites W2468887307 @default.
• W3021137551 cites W2469348535 @default.
• W3021137551 cites W2511931103 @default.
• W3021137551 cites W2528656877 @default.
• W3021137551 cites W2576909235 @default.
• W3021137551 cites W2783102394 @default.
• W3021137551 cites W2788298916 @default.
• W3021137551 cites W2801138925 @default.
• W3021137551 cites W2883573514 @default.
• W3021137551 cites W2902483061 @default.
• W3021137551 cites W2907801841 @default.
• W3021137551 cites W2934013272 @default.
• W3021137551 cites W2941313684 @default.
• W3021137551 cites W2945421709 @default.
• W3021137551 cites W2953115273 @default.
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• W3021137551 doi "https://doi.org/10.1002/acn3.51050" @default.
• W3021137551 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7261760" @default.
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