Basic concepts of medical genetics. Formal genetics, part 4

Abstract

Non-traditional/non-classical/non-Mendelian patterns of inheritance refer to different modes of transmission of genetic diseases that are not caused by single mutant genes. These diseases include a wide variety of genetically-determined disorders, e.g., polygenic diseases/chromosomal aberrations/ mitochondrial disorders and multifactorial diseases. Non-traditional inheritance patterns are not compatible with the rules of inheritance that characterize the transmission of single gene disorders since they differ from each other in many respects like rates of occurrence, recurrence risk, sex predilection, spectrum of phenotypic variation and many others. The characteristics of these non-traditional patterns are dependent solely on the nature of the disease as regards its etiology and the specific pathogenetic mechanism(s) underlying its development. Recognition of these different inheritance patterns is important for the provision of proper counseling advice because they have different recurrence risks and different clinical and management implications. Non-traditional patterns of inheritance characterize diseases caused by specific pathogenetic mechanisms that include: defective genetic imprinting, uniparental disomy, nucleotide repeat expansion (tri/tetra/penta/ hexa-nucleotide repeat expansion), mutations of mitochondrial genome, mutations caused by combined multifactorial (genetic/environmental) effects, mosaicism, chromosomal aberrations, microdeletion/microduplication/microtriplication defects and polygenic defects [1] (Table 1). 1. Genetic imprinting