In hereditary spherocytosis mutation, not seen is?
**Core Concept**
Hereditary spherocytosis (HS) is a genetic disorder characterized by the production of abnormal, sphere-shaped red blood cells (spherocytes) due to mutations in genes encoding proteins of the red blood cell membrane. The primary defect is in the spectrin-actin cytoskeleton, leading to reduced red blood cell deformability and increased risk of hemolysis.
**Why the Correct Answer is Right**
The correct answer is related to the genetic mutations underlying hereditary spherocytosis. The condition is typically caused by mutations in one of four genes: ANK1 (encoding ankyrin), SPTB (encoding beta-spectrin), SPTA1 (encoding alpha-spectrin), or EPB42 (encoding protein 4.2). These mutations disrupt the normal interaction between spectrin and the red blood cell membrane, leading to the characteristic spherocytic shape.
**Why Each Wrong Option is Incorrect**
* **Option A:** Not applicable, as this option is blank.
* **Option B:** Not seen in hereditary spherocytosis is an increase in red blood cell membrane surface area, as the mutations typically lead to a decrease in membrane surface area due to spectrin-actin cytoskeleton defects.
* **Option C:** Not seen in hereditary spherocytosis is a mutation in the HBB gene, which encodes the beta-globin subunit of hemoglobin. Hereditary spherocytosis is primarily related to defects in the red blood cell membrane, not hemoglobin.
* **Option D:** Not seen in hereditary spherocytosis is a decrease in red blood cell membrane surface area, as the mutations typically lead to an increase in membrane surface area due to spectrin-actin cytoskeleton defects.
**Clinical Pearl / High-Yield Fact**
A key clinical feature of hereditary spherocytosis is the presence of target cells on peripheral smear, which are indicative of the underlying membrane defects. Target cells are typically seen in conditions characterized by membrane instability or disorders of the spectrin-actin cytoskeleton.
**Correct Answer:** D.