Identification of FMR2, a novel gene associated with the FRAXE CCG repeat and CpG island

Nat Genet. 1996 May;13(1):109-13. doi: 10.1038/ng0596-109.


Five folate-sensitive fragile sites have been identified at the molecular level to date. Each is characterized by an expanded and methylated trinucleotide repeat CGG (CCG). Of the three X chromosome sites, FRAXA, FRAXE and FRAXF, the former two are associated with mental retardation in their expanded forms. FRAXA expansion results in fragile X syndrome due to down regulation of expression of the FMR1 gene, which carries the hypermutable CGG repeat in the 5' untranslated portion of its first exon. Mild mental retardation without consistent physical findings has been found associated with expanded CCG repeats at FRAXE. We have identified a large gene (FMR2) transcribed distally from the CpG island at FRAXE, and down-regulated by repeat expansion and methylation. The gene is novel, expressed in adult brain and placenta, and shows similarity with another human protein, MLLT2, expressed from a gene at chromosome 4q21 involved in translocations found in acute lymphoblastic leukaemia (ALL) cells. Identification of this gene will facilitate further studies to determine the role of its product in FRAXE associated mental deficiency.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Brain / metabolism
  • Chromosomes, Human, Pair 4*
  • Cloning, Molecular
  • DNA Primers
  • Dinucleoside Phosphates
  • Female
  • Fragile X Syndrome / genetics*
  • Gene Expression*
  • Humans
  • Intellectual Disability / genetics*
  • Molecular Sequence Data
  • Nuclear Proteins*
  • Organ Specificity
  • Placenta / metabolism
  • Polymerase Chain Reaction
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Pregnancy
  • Protein Biosynthesis
  • Proteins / genetics*
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Repetitive Sequences, Nucleic Acid*
  • Sequence Homology, Amino Acid
  • Trans-Activators*
  • Transcription, Genetic
  • X Chromosome*


  • AFF2 protein, human
  • DNA Primers
  • Dinucleoside Phosphates
  • Nuclear Proteins
  • Proteins
  • RNA, Messenger
  • Trans-Activators
  • cytidylyl-3'-5'-guanosine

Associated data

  • GENBANK/AC002368