The Genetics of the Amyloidoses
▪ Abstract The amyloidoses are diseases in which abnormalities in the secondary structure of precursor proteins result in decreased solubility under physiologic conditions, with subsequent organ compromise. A total of 18 proteins have been definitively identified as amyloid precursors associated with human disease. Mutations in the genes that encode some of these proteins produce autosomal dominant disease in mid to late adult life. Until recently, the late onset has obscured the familial nature of some of the disorders. This is especially true in the apparently sporadic diseaseproducing deposits found even later in life. In many instances, these deposits are derived from precursors encoded by wild-type genes (perhaps influenced by alleles that are polymorphic in the normal population); in other cases, they represent autosomal dominant disease with age-dependent penetrance. The genetic aspects of amyloid diseases produced by the deposition of four different proteins have been investigated in detail and provide insights into the particular diseases and amyloidogenesis in general.