USMLE (United States Medical Licensing Examination) Step 1 Practice Exam

Which mutations are associated with Tuberous Sclerosis?

1. Heart defects in AV valves

2. Tuberin and harmartin mutations

3. Seizures

4. Rhabdomyoma

The correct answer is: Tuberin and harmartin mutations

Tuberous sclerosis is a genetic disorder characterized by benign tumors in various organs, including the brain, kidneys, heart, and skin. The condition is primarily caused by mutations in two key genes: TSC1 and TSC2. The TSC1 gene encodes a protein called hamartin, while the TSC2 gene encodes tuberin. Mutations in these genes disrupt the regulation of cell growth and proliferation, leading to the formation of hamartomas, which are the hallmark of tuberous sclerosis. Therefore, identifying mutations in the TSC1 or TSC2 genes—resulting in the inadequate production or functional impairment of hamartin and tuberin—is directly linked to the development of tuberous sclerosis. This connection highlights the importance of these genetic alterations in the pathology of the disease, which is why mutations in tuberin and hamartin are considered the primary genetic defects associated with tuberous sclerosis. In contrast, while heart defects, seizures, and rhabdomyomas are clinical manifestations often seen in patients with tuberous sclerosis, they do not directly represent the genetic mutations that cause the disease. Heart defects are related to other congenital issues; seizures can occur due to neurological involvement but are not causative