If you were to look up Gaucher disease on the OMIM website, you would see that there are three major types, designated Type I (OMIM 230800), Type II (OMIM 230900), and Type III (OMIM 231000). All three types are mutations of the gene for acid-β-glucosidase, encoded on chromosome 1. Different mutations of this gene produce the three types of Gaucher disease that differ somewhat in their symptoms and disease severity.

Thinking about the production or function of the acid-β-glucosidase enzyme, why do you suppose different mutations of this gene produce differences in symptoms and disease severity?

Key Concepts

Gene Mutations

Gene mutations are changes in the DNA sequence of a gene that can affect the function of the protein it encodes. In the case of Gaucher disease, mutations in the gene for acid-β-glucosidase lead to variations in enzyme activity. These mutations can result in either a complete loss of function or a partial reduction in enzyme activity, which directly influences the severity and type of symptoms experienced by individuals.

Enzyme Function

Enzymes are biological catalysts that speed up chemical reactions in the body. Acid-β-glucosidase is responsible for breaking down glucocerebroside into glucose and ceramide. Variations in the enzyme's activity due to different mutations can lead to the accumulation of glucocerebroside, causing the diverse symptoms associated with the different types of Gaucher disease, such as organ enlargement and bone pain.

Phenotypic Variation

Phenotypic variation refers to the observable differences in traits among individuals, which can arise from genetic differences and environmental factors. In Gaucher disease, the specific mutations in the acid-β-glucosidase gene lead to varying levels of enzyme activity, resulting in different clinical manifestations and severities of the disease. This variation is crucial for understanding how genetic mutations can influence health outcomes.