In terms of autosomal dominant disorders, what is the second mechanism listed?

• A. Haploinsufficiency
• B. Gain-of-function mutations
• C. Loss-of-function mutations
• D. Polygenic inheritance

Answer: (B)

In the context of autosomal dominant disorders, gain-of-function mutations represent a significant mechanism of pathogenesis. Autosomal dominant disorders typically arise from a mutation in one copy of a gene that causes a dominant phenotype, which can occur through various mechanisms, with gain-of-function mutations being one of them.

Gain-of-function mutations lead to an altered protein that enhances its function or gives the protein a new, often harmful function. This can result in overactivity of signaling pathways or the production of proteins that interfere with normal cellular function. An example of this is the mutation in the FGFR3 gene that causes achondroplasia, where an altered fibroblast growth factor receptor negatively affects bone growth.

While haploinsufficiency, which involves losing function due to having only one functional copy of a gene, and loss-of-function mutations, which directly reduce or eliminate gene product function, are also relevant mechanisms for certain conditions, they do not define the second mechanism in the context of autosomal dominant inheritance as broadly as gain-of-function mutations do. Polygenic inheritance, on the other hand, refers to traits influenced by multiple genes and is not a mechanism exclusive to dominant disorders. Thus, the prominence and specificity of gain-of-function mutations as a mechanism in autosomal dominant