Reduced penetrance in human inherited disease

Abstract EN

For many inherited diseases, the same mutation is not always expressed in all persons who carry it, moreover, when the mutation is expressed, it is not always expressed in the same way.

These findings are the basis for the concepts of penetrance and expressivity.

Understanding the factors that control penetrance of disease genes will provide insight into the fundamental disease processes and will help in genetic counselling.

With the advancement of molecular genetics over the last few years, some of the underlying mechanisms of reduced penetrance have been elucidated.

These include, mutation type, allelic variations in gene expression, epigenetic factors, gene-environment interplay, influence of age and sex, allele dosage, oligogenic and digenic inheritance mutations, modifier genes, copy number variations as well as the influence of additional gene variants and the effect of single nucleotide polymorphisms.