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*Repeat Expansion Diseases - Coggle Diagram

- - - - Normal: CGG, n < 55
      - Permutation: CGG, 55 < n < 200
      - Full Mutation: CGG, n > 200
    - - ~1/3500 in males
      - ~1/6000 in females
      - Expanded CGG repeats lead to hypermethylation and transcriptional shutdown
      - FMRP protein loss
        
        Results in increased production of glutamate receptors in synapses
        
        Results in loss of ability to regulate synaptic biology
    - - Intellectual Disability
      - ASD
      - Elongated faces and long ears
      - Macroorchidism (large testicles)
      - FXTAS is preemptive to FXS
        
        males: Tremor, ataxia
        
        females: primary ovarian insufficiencies
  - - - Myotonia (Not being able to let go of the bar or things like that) is pathognomonic of DM
        
        Jaw and slurring of words
        
        Neck myotonia which causes a lot of pain as the back muscles need to hold up your head
        
        Joint issues
      - The whole family is kinda diagnosed at once after one member is diagnosed with that.
      - Arrhythmia can be an issue with myotonic dystrophy (is the most common cause of death; pacemakers, etc. can help with that)
      - Cararacts are also a good thought
      - Hypersomnia (need to sleep) makes so many things more difficult (CNS symptom)
      - Anxiety and depression
      - Mental acuity and anger are common
      - Memory difficulties remembering things
    - - Normal: n = 5-30
      - Mildly affected: n = 50-80
      - Severely affected: n > 2000
      - Repeat length correlates with age of onset
    - - Expanded CTG repeat
      - Transcribed into expanded CUG repeats
        
        CUG repeat expression in a different gene can reproduce DM features
      - Sequestration to MBNL Proteins which reduces functionality of MBNL
        
        MBNL regulates alternative splicing on the ClC1 pre-mRNA which causes a nonsense mediated decay of the ClC1 protein which affects muscle function. MBNL helps to alternatively splice out an unnecessary exon that has a stop codon. Hence its loss leading to nonsense mutations of the protein
      - Widespread changes in MBNL-mediated RNA splicing and RNA metabolism
  - - - Expanded CAG repeats (>35)
      - Transcribed and translated into polyglutamine repeats
      - Myriad downstream consequences (protein aggregates, etc.)
      - Cell death (dramatic loss of striatal neurons in brain)
    - - Motor (chorea of the face, trunk and limbs)
      - Cognitive (Executive dysfunction, difficulty searching memory)
      - Psychiatric (depression, anxiety, apathy, etc.; increased risk for suicide)
  - - - Fragile X
      - Friedreigh's Ataxia
    - - Myotonic Dystrophy
      - Huntington's
      - Fragile X associated Tremor/Ataxia Syndrome
      - Fuch's Endothelial Corneal Dystrophy
      - C9ORF72/ALS/FTD
    - - Huntington's
      - C9ORF72/ALS/FTD
      - Some Spinocerebellar Ataxias
  - - - Dementia (memory impairment, personality change, language dysfunction)
      - Limb onset
        
        Weakness, Spasticity, muscle atrophy, fasciculations
      - Bulbar onset
        
        slow speech, jaw jerk reflex, facial weakness, tongue atrophy/fasciculations