[Mechanisms and consequences of genetic mutations]

Identification of mutations responsible for human monogenic hereditary diseases has lately undergone rapid development. It is now possible to establish the mutation spectrum for a given genetic disease and international databases are now available on the Internet. New mutational mechanisms have been identified:transposition, inversion, trinucleotide repeat expansion. At the disease level, knowledge of molecular defects has allowed to better delimit mechanisms of gain or loss of function, to understand dominant or recessive mode of inheritance, to explain anticipation phenomena, to identify founder effect amid a selected population, to establish, in some privileged cases, phenotype-genotype correlations and above all to elicit allelic and genetic heterogeneity hitherto unsuspected. Identification of deleterious mutations is also the basis of diagnosis at the gene level which today has a growing impact on genetic counselling and prenatal diagnosis.