Genetics and physiopathology of X-linked mental retardation

Mutations in X-linked genes account for an excess of males affected with mental retardation. Target genes have recently been identified both for syndromic forms of X-linked mental retardation and in families affected with "nonspecific" forms, where cognitive impairment is the only clinical feature. The latter are genetically very heterogeneous, as the eight genes identified up to know account for only a minority of affected families. Proteins that have a role in chromatin remodelling are affected in three important syndromic forms, while defects in signal transduction pathways implicated in neuronal maturation were found in "nonspecific" forms. These findings provide important insights into the molecular and cellular defects that underlie mental retardation.