Gaucher Disease Phenotypes Outflanked?
- Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037 USA
This extract was created in the absence of an abstract.
One of the major puzzles in modern human genetics is the fact that patients with the same genotype for a disease-causing mutation may express very different clinical manifestations. Gaucher disease is one of the more common, clinically important, autosomal recessive disorders. In this issue, Winfield et al. (1997) point out that the problem of phenotypic variation is a serious one in this disorder and that understanding the cause of this variation is of great practical importance. Our ability to provide useful prenatal counseling is hampered by the variability of outcome, even when the genotype of the fetus has been established.
The identification of three new genes close to the glucocerebrosidase (GBA) locus enriches our understanding of this important area of chromosome 1. But whether the presence of important genes adjacent to the GBA locus can explain the variability of the manifestations of Gaucher disease raises two distinct questions: The first concerns the cause of the variation that exists between individuals with the same genotype; and the second relates to the cause of the variation between patients who have different Gaucher disease genotypes. The first of these questions—patients with the same genotype—is the most vexing, because the difference between clinical expression of patients with different genotypes seems related, at least in part, to the severity of the glucocerebrosidase deficiency produced.
To explain the differences between individuals who have the sameGBA genotype we must consider the fact that such differences can occur within the context of three different circumstances: (1) in identical twins, in which case …
