FIGURE 2.

Age-related penetrance of monogenic alleles (mutations). The x-axis shows the age of disease manifestation in years. Characteristic features of age-related penetrance are shown for AR versus AD CKD genes. For example, the median age of onset for a homozygous truncating mutation (‘strong allele’) in an AR gene may occur at 10 years of age (dark blue curve). For another individual with a homozygous missense mutation in the same disease gene (‘mild allele’), the age-of-onset curve may be skewed to a later median age of onset (light blue curve). Similar to AR genes, AD genes show age-related penetrance. As a tendency, AD disease genes manifest later in life. In addition, AD disease genes feature effects such as incomplete penetrance (i.e. a mutation carrier never manifesting with disease) and variable expressivity (i.e. varied organ involvement between carriers of an identical mutation), which are usually not seen in AR acting genes. Exposure to environmental risk factors can hasten disease onset (red arrow), while treatment or prophylaxis can delay the onset of disease (green arrow).