Contribution of genetics to knowledge and management of hereditary renal diseases progressing to renal failure

Genes of most of the hereditary renal diseases progressing to renal insuffi ciency are now identified. In the first part of this paper we describe thei r multi-faceted genetics. Genetic heterogeneity has been demonstrated in ma ny of these diseases, such as Alport's syndrome and nephronophtisis. In som e of them an allelic heterogeneity is present as in the X-linked form of Al port's syndrome (more than 300 different mutations have been described alon g the COL4A5 gene). Besides these classical mendelian diseases, mendelian s ubentities have been isolated within common diseases such as cortico-resist ant nephrosis. Many diseases also demonstrate a variability of their phenot ype resulting from allelic and/or genetic heterogeneity, or from modifier g enes. In the second part of the paper we discuss the consequences of this e xplosion of knowledge with respect to epidemiology, genetic diagnosis, pren atal diagnosis and treatment. (C) 2001 Editions scientifiques et medicales Elsevier SAS.