Question

Describe the mutations in monogenic autoinflammatory diseases with examples.

Hint:

Monogenic autoinflammatory diseases are typically inherited in an autosomal dominant manner and are caused by mutations in genes involved in regulating innate immunity.

Answer 1

Step 1: Overview of Monogenic Autoinflammatory Diseases.
Monogenic autoinflammatory diseases are caused by mutations in single genes that affect the regulation of the innate immune system, leading to spontaneous and recurrent episodes of inflammation.
Step 2: Key Mutations and Examples.
- Familial Mediterranean Fever (FMF): Caused by mutations in the MEFV gene, which codes for the protein pyrin. This results in uncontrolled activation of the inflammasome.
- Hyper-IgD Syndrome (HIDS): Caused by mutations in the MVK gene, which leads to a defect in mevalonate kinase, an enzyme involved in cholesterol biosynthesis.
- Cryopyrin-Associated Periodic Syndromes (CAPS): Caused by mutations in the NLRP3 gene, leading to an overactive inflammasome and excessive production of pro-inflammatory cytokines.
Step 3: Pathophysiology.
These mutations cause dysregulated immune responses, leading to systemic inflammation and the characteristic symptoms of each disease, such as fever, rashes, and arthritis.