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Updated: Dec 25 2018

Trinucleotide Repeat Expansion Diseases

  • Overview
      • Disease
      • Nucleotide Repeat
      • Gene affected
      • Chromosome
      • Fragile X syndrome
      • CGG
      • FMR1
      • Sex X chromosome
      • Friedrich ataxia
      • GAA
      • FXN
      • 9
      • Huntington's disease
      • CAG
      • HTT
      • 4
      • Myotonic dystrophy - type 1
      • CTG
      • DMPK
      • 19
  • Fragile X Syndrome
    • Inheritance pattern
      • X-linked dominant
    • Repeat expansion
      • CGG repeat on FMR1 gene
    • Presentation
      • mental retardation
      • autism
      • long face large jaw
      • large ears
      • large testicles (macroorchidism)
  • Friedrich's Ataxia
    • Inheritance pattern
      • autosomal recessive
    • Repeat expansion
      • GAA repeat on chromosome 9
        • results in
          • defect in frataxin (an iron binding protein) that leads to impaired mitochondrial function
          • degeneration of various spinal cord tracts
    • Presentation
      • neurological findings
        • muscle weakness
        • loss of deep tendon reflexes
        • loss of vibratory sensation and proprioception
        • clumsy gait with falls, nystagmus
      • other findings
        • pes cavus
        • diabetes mellitus
        • hypertrophic cardiomyopathy
  • Huntington's Disease
    • Inheritance pattern
      • autosomal dominant
    • Repeat expansion
      • CAG repeat on chromosome 4
    • Presentation
      • neurologic findings
        • caudate atrophy with enlarged ventricles on head CT
        • decreased GABA and Ach
        • increased dopamine
        • NMDA mediated excitotoxicity
        • movement disorder
        • aggression/pyschosis
        • depression
        • dementia
        • occurs typically a young patient (age 20 - 50)
    • mnemonic
      • HUNT 4 an animal, put it in a CAGe
  • Myotonic Dystrophy - Type 1
    • Inheritance pattern
      • autosomal dominant
    • Repeat expansion
      • CTG repeat on DMPK gene
        • results in
          • abnormal expression of myotonin protein kinase
    • Presentation
      • myotonia
      • muscle wasting
      • cataracts
      • testicular atrophy
      • arrhythmia
      • frontal balding
      • classically "can't release a doorknob/handshake"
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