X-linked genetic disorder of the membrane-associated protein DYSTROPHIN

A disease of muscle structure

(Duchenne Muscular Dystrophy is the most common form)

Autoimmune attack mediated by autoantibodies against ACh receptors

A disease of neuromuscular junctions

Results in progressive lost of neuromuscular control

Attributes: Widened synaptic cleft, decreased number of ACh receptors, postsynaptic membrane surface area decreasesd

• Infancy
• Failure to Thrive
• Hepatomegaly
• Nonketotic Hypoglycemia

• Most common
• Mild myopathy in childhood

• Very rare
• Some infants: failure to thrive, nonketotic hypoglycemia
• Mild myopathy in a few patients

• Two forms: CPT-I, CPT-II
• Autosomal recessive
• Typically no family history
• Rare

Molecular Pathology of

Hemophilia

Deletion of Entire Structural Gene

(Factor VIII)

Molecular Pathology of

β-Thalassemia

Deletion of Entire Structural Gene

Major - Lethal, affects both β globin genes

Minor - Mild, microcytic anemia, affects only one β globin gene

 Molecular Pathology of

Duchenne Muscular Dystrophy

& Becker Muscular Dystrophy

Partial Gene Deletion

Dystrophin gene (X-linked)

DMD: Out-of-frame deletion (more severe)

Becker: In-frame deletion (less severe)

Exon duplication in 5% of cases

Molecular Pathology of

Fragile X,

Myotonic Dystrophy,

and Huntington's

Insertion or Amplification of DNA Sequences

Specifically, polymorphic triplet repeats

Fragile X: CGG

Myotonic Dystrophy: CTG

Huntington's: CAG

Molecular Pathology of

Certain Cancers

(Colerectal, Gastric,

and Endometrial Carcinomas)

Microsatellite Instability

Defective mismatch repair (MMR) gene

Molecular Pathology of

Alu Elements

Insertion of Sequences within a Gene

Alu elements may "jump" into a coding sequence (lethal)

Molecular Pathology of

Cystic Fibrosis (CF)

Codon Deletion

Loss of residue Phe-508 in the cystic fibrosis transmembrane regulator (CFTR)

Detected by PCR

Molecular Pathology of

Ehlers-Danlos Syndrome

Point Mutation

Prevention of Posttranscriptional Processing

Results in hyper-mobility of joints

Loss of exon 6 (COL1A2 gene: α2 chain of procollagen)

Autosomal dominant

Molecular Pathology of

Factor V Leiden Mutation

Point Mutation

Loss of proteolytic cleavage site (prevents inactivation of Factor Va)

Associated with 90% of DVT