Table 1.

The Porphyrias Illustrate Many Genetic Principles

1. Multiple Modes of Inheritance:

Autosomal Dominant (AIP, HCP, & VP) & Recessive (AHPs, CEP, & EPP)

X-Linked (XLP, Rarely CEP)

Rare Homozygous Dominant Types (AIP, HCP, & VP)

Sporadic/Acquired (PCT)

Prevalence & Penetrance (AHPs)

2. Multiple Mutations Causing Each Disease (All)

Loss- or Gain-of-Function Mutations (All)

Common Low Expression Allele (EPP)

Regulation of Heme Biosynthesis & Regulatory Mutations

Negative Feedback Repression (AHPs)

Variable Expressivity (All)

Genotype/Phenotype Correlations (CEP)

Benign Variants (All)

3. X-Chromosomal Inactivation (XLP)

4. Modifying Genes Responsible for Expression & Severity (AHPs, EPP)

5. Pharmacogenetic/Ecogenetic Disorders (AHPs)