A mutation in the Rett syndrome gene, MECP2, causes X-linked mental retardation and progressive spasticity in males

Heterozygous mutations in the X-linked MECP2 gene cause Rett syndrome, a se vere neurodevelopmental disorder of young females. Only one male presenting an MECP2 mutation has been reported; he survived only to age 1 year, sugge sting that mutations in MECP2 are male lethal. Here we report a three-gener ation family in which two affected males showed severe mental retardation a nd progressive spasticity, previously mapped in Xq27.2-qter. Two obligate c arrier females showed either normal or borderline intelligence, simulating an X-linked recessive trait. The two males and the two obligate carrier fem ales presented a mutation in the MECP2 gene, demonstrating that, in males, MECP2 can be responsible for severe mental retardation associated with neur ological disorders.