Hereditary spherocytosis is an autosomal dominant condition most often related to deficiency of which protein?

Hereditary spherocytosis is an autosomal dominant condition most often related to deficiency of which protein?

• A. Ankyrin
• B. Band 3
• C. Actin
• D. Spectrin

Answer: (D)

Hereditary spherocytosis occurs when the red cell cytoskeleton that anchors the plasma membrane is defective, leading to loss of membrane surface area and the formation of spheres that are less deformable. The most common protein involved is spectrin, the major cytoskeletal scaffold that forms a lattice under the membrane and connects to the membrane via ankyrin and band 3. A deficiency or dysfunction of spectrin weakens these vertical membrane–cytoskeleton connections, causing RBCs to become spherocytes, get trapped in the spleen, and undergo hemolysis. The condition is typically inherited in an autosomal dominant pattern. While deficiencies in ankyrin or band 3 can also cause similar membrane instability, spectrin deficiency is the classic, most frequent culprit. Actin is part of the cytoskeleton but its deficiency is not the typical driver of this disorder.

Hereditary spherocytosis occurs when the red cell cytoskeleton that anchors the plasma membrane is defective, leading to loss of membrane surface area and the formation of spheres that are less deformable. The most common protein involved is spectrin, the major cytoskeletal scaffold that forms a lattice under the membrane and connects to the membrane via ankyrin and band 3. A deficiency or dysfunction of spectrin weakens these vertical membrane–cytoskeleton connections, causing RBCs to become spherocytes, get trapped in the spleen, and undergo hemolysis. The condition is typically inherited in an autosomal dominant pattern. While deficiencies in ankyrin or band 3 can also cause similar membrane instability, spectrin deficiency is the classic, most frequent culprit. Actin is part of the cytoskeleton but its deficiency is not the typical driver of this disorder.