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

TitleIdentification of FMR2, a novel gene associated with the FRAXE CCG repeat and CpG island.
Publication TypeJournal Article
Year of Publication1996
AuthorsGu, Y, Shen, Y, Gibbs, RA, Nelson, DL
JournalNat Genet
Volume13
Issue1
Pagination109-13
Date Published1996 May
ISSN1061-4036
KeywordsAdult, Amino Acid Sequence, Base Sequence, Brain, Chromosomes, Human, Pair 4, Cloning, Molecular, Dinucleoside Phosphates, DNA Primers, Female, Fragile X Syndrome, Gene Expression, Humans, Intellectual Disability, Molecular Sequence Data, Nuclear Proteins, Organ Specificity, Placenta, Polymerase Chain Reaction, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Pregnancy, Protein Biosynthesis, Proteins, Repetitive Sequences, Nucleic Acid, RNA, Messenger, Sequence Homology, Amino Acid, Trans-Activators, Transcription, Genetic, X Chromosome
Abstract

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.

DOI10.1038/ng0596-109
Alternate JournalNat. Genet.
PubMed ID8673086
Grant ListHD29251 / HD / NICHD NIH HHS / United States
HG00210 / HG / NHGRI NIH HHS / United States
HG00823 / HG / NHGRI NIH HHS / United States