What condition is caused by a base substitution mutation?

Sickle cell anemia is directly caused by a base substitution mutation, which is a type of point mutation. In this condition, a single nucleotide in the DNA sequence is altered—specifically, adenine (A) is replaced by thymine (T) in the gene that encodes for the beta chain of hemoglobin. This single change leads to the substitution of valine for glutamic acid in the hemoglobin protein. As a result, the altered hemoglobin (known as hemoglobin S) causes red blood cells to deform into a sickle shape under low oxygen conditions, leading to complications such as blockages in blood vessels and reduced oxygen transport.

In contrast, conditions like hemophilia and cystic fibrosis can arise from various mutations including deletions or large chromosomal abnormalities, while Down syndrome is specifically caused by an additional copy of chromosome 21, rather than a point mutation. Thus, the direct link between base substitution and sickle cell anemia makes it the correct choice.