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

Am J Hum Genet. 2000 Oct;67(4):982-5. doi: 10.1086/303078. Epub 2000 Sep 12.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Child, Preschool
  • Chromosomal Proteins, Non-Histone*
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • Dosage Compensation, Genetic
  • Female
  • Fetal Death / genetics
  • Genes, Lethal / genetics
  • Genes, Recessive / genetics
  • Genetic Linkage / genetics*
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Intellectual Disability / complications
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Male
  • Methyl-CpG-Binding Protein 2
  • Muscle Spasticity / complications
  • Muscle Spasticity / genetics*
  • Muscle Spasticity / physiopathology
  • Mutation / genetics*
  • Pedigree
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Repressor Proteins*
  • Rett Syndrome / complications
  • Rett Syndrome / genetics*
  • Rett Syndrome / physiopathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • X Chromosome / genetics*

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • RNA, Messenger
  • Repressor Proteins