Trinucleotide Repeat Disorders Lecture Notes

Introduction

• Trinucleotide repeat disorders occur when a trinucleotide sequence is repeated many times within a gene.
• Example: CAG sequence repeating 10 to 200 times.
• These disorders do not follow Mendel's laws of inheritance (non-Mendelian disorders).

Key Examples of Trinucleotide Repeat Disorders

1. Huntington's Disease
2. Fragile X Syndrome
3. Friedrich's Ataxia
4. Myotonic Dystrophy

Trinucleotide Repeats in Disorders

• Huntington's Disease: CAG repeats
• Fragile X Syndrome: CGG repeats
• Friedrich's Ataxia: GAA repeats (associated with gait problems)
• Myotonic Dystrophy: CTG repeats

Fragile X Syndrome

• Inheritance: X-linked recessive
• Mainly Affected: Males
• Chromosome Appearance: Fragile end of X chromosome due to non-staining portions.
• Gene Mutation: FMR1 (Familial Mental Retardation gene)
  • Less than 55 CGG repeats considered normal.
  • 55-200 repeats: Pre-mutation (Fragile X tremors)
  • More than 200 repeats: Fragile X Syndrome
• Clinical Features:
  • Long face, long ears, large mandible, normal nose
  • Post-pubertal macroorchidism (large testes)
  • Cardiovascular: Mitral valve prolapse
  • Females: Often carriers, possible premature ovarian failure
• Sherman's Paradox: Anticipation with increased repeats and disease severity over generations.

Myotonic Dystrophy

• Inheritance: Autosomal dominant
• Trinucleotide Repeat: CTG repeats
• Clinical Features:
  • Difficulty in releasing grip
  • Christmas tree cataracts
  • Hatchet faces, frontal balding (male pattern)
  • Testicular atrophy
  • Muscular atrophy, potential respiratory difficulties
  • Cardiomyopathies leading to heart blocks and arrhythmias

Summary

• Discussed Fragile X Syndrome and Myotonic Dystrophy in detail.
• Next topics: Huntington's Disease and Friedrich's Ataxia in subsequent videos.

• Note: These notes cover the key aspects of trinucleotide repeat disorders, focusing on Fragile X Syndrome and Myotonic Dystrophy including their clinical features, inheritance patterns, and associated genetic mutations.