A mutation hot spot for nonspecific X-linked mental retardation in the MECP2 gene causes the PPM-X syndrome

Am J Hum Genet. 2002 Apr;70(4):1034-7. doi: 10.1086/339553. Epub 2002 Feb 15.


We report here the genetic cause of the X-linked syndrome of psychosis, pyramidal signs, and macro-orchidism (PPM-X) in a three-generation family manifesting the disorder as a mutation in the methyl-CpG binding-protein 2 (MECP2) gene in Xq28. The A140V mutation was found in all affected males and all carrier females in the family. To date, descriptions have been published of two patients with independent familial mental retardation (MR) and two patients with sporadic MR who harbor this specific mutation in the MECP2 gene. This strongly suggests that A140V is a hot spot of mutation resulting in moderate to severe MR in males. A simple and reliable PCR approach has been developed for detection of the hot spot A140V mutation to prescreen any other unexplained cases of MR before further extensive mutation analyses.

MeSH terms

  • Base Sequence
  • Chromosomal Proteins, Non-Histone*
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Linkage / genetics*
  • Humans
  • Intellectual Disability / complications
  • Intellectual Disability / genetics*
  • Male
  • Methyl-CpG-Binding Protein 2
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Polymorphism, Restriction Fragment Length
  • Psychotic Disorders / complications
  • Psychotic Disorders / genetics*
  • Repressor Proteins*
  • Syndrome
  • X Chromosome / genetics*


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

Associated data

  • GENBANK/X99686
  • OMIM/MIM300055
  • OMIM/MIM312750