Yleistynyt amylomyotrofia

Retinan  regulatiivisen genomin säätelygeenien joukosta  TCF4  omaa  onkogeenisyyden alueella assoisaatiota  yleistyneeseenamyotrofiaan ja mm. geeniin VAMP1. https://www.genecards.org/cgi-bin/carddisp.pl?gene=TCF4&keywords=TCF4

Generalized amyotrophy HP:0003700

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Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.

Hierarchy

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• Skeletal muscle atrophy
• Generalized amyotrophy
  • Generalized limb muscle atrophy

Synonyms:    Diffuse amyotrophy, Diffuse muscle atrophy, Diffuse muscle wasting, Diffuse skeletal 

 

muscle wasting, Generalised amyotrophy, Generalised muscle atrophy, Generalised muscle degeneration, Generalized muscle atrophy, Generalized muscle degeneration, Muscle atrophy, diffuse, Muscle atrophy, generalised, Muscle atrophy, generalized, Muscular atrophy, generalised, Muscular atrophy, generalized

OMIM:610006  2-Methylbutyryl-Coa dehydrogenase deficiency ACADSB [36 ]

 
ORPHA:466794Acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome SCYL1 [57410 ]

 
OMIM:300523 Allan-Herndon-Dudley syndrome SLC16A2 [6567 ]

 
ORPHA:79279 Alpha-N-acetylgalactosaminidase deficiency type 1 NAGA [4668 ]

 
ORPHA:157954 ANE syndrome RBM28 [55131 ]

 
ORPHA:251282 Autosomal dominant spastic ataxia type 1, VAMP1 [6843 ]

Gene Location: 12p13.31

Definition
Synapotobrevins, syntaxins, and the synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Mutations in this gene are associated with autosomal dominant spastic ataxia 1. Multiple alternative splice variants have been described, but the full-length nature of some variants has not been defined. [provided by RefSeq, Jul 2014]

 

 Onko  jotain yhteyttä  VAMP1 geenin jollain  geenimutaatiolla  aikuisuudessa ilmenevään amyotrofiseen lateroskleroosiin?

 

HAKU PubMwd  

Neuronal overexpression of human VAPB slows motor impairment and neuromuscular denervation in a mouse model of ALS.

Kim JY, Jang A, Reddy R, Yoon WH, Jankowsky JL. Hum Mol Genet. 2016 Nov 1;25(21):4661-4673. doi: 10.1093/hmg/ddw294. PMID: 28173107 Free PMC article.

 

Four mutations in the VAMP/synaptobrevin-associated protein B (VAPB) gene have been linked to amyotrophic lateral sclerosis (ALS) type 8. The mechanism by which VAPB mutations cause motor neuron disease is unclear, but studies of the most common P56S variant suggest both loss of function and dominant-negative sequestration of wild-type protein. Diminished levels of VAPB and its proteolytic cleavage fragment have also been reported in sporadic ALS cases, suggesting that VAPB loss of function may be a common mechanism of disease. Here, we tested whether neuronal overexpression of wild-type human VAPB would attenuate disease in a mouse model of familial ALS1. We used neonatal intraventricular viral injections to express VAPB or YFP throughout the brain and spinal cord of superoxide dismutase (SOD1) G93A transgenic mice. Lifelong elevation of neuronal VAPB slowed the decline of neurological impairment, delayed denervation of hindlimb muscles, and prolonged survival of spinal motor neurons. Collectively, these changes produced a slight but significant extension in lifespan, even in this highly aggressive model of disease. Our findings lend support for a protective role of VAPB in neuromuscular health.