Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome

• Published in: Cell Vol. 65; no. 5; pp. 905 - 914
• Main Authors: Verkerk, Annemieke J.M.H., Pieretti, Maura, Sutcliffe, James S., Fu, Ying-Hui, Kuhl, Derek P.A., Pizzuti, Antonio, Reiner, Orly, Richards, Stephen, Victoria, Maureen F., Zhang, Fuping, Eussen, Bert E., van Ommen, Gert-Jan B., Blonden, Lau A.J., Riggins, Gregory J., Chastain, Jane L., Kunst, Catherine B., Galjaard, Hans, Thomas Caskey, C., Nelson, David L., Oostra, Ben A., Warren, Stephen T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.05.1991
• Subjects: Alleles; Amino Acid Sequence; Base Sequence; Blotting, Northern; Brain - metabolism; Cosmids; DNA - genetics; DNA - isolation & purification; Exons; Fragile X Mental Retardation Protein; Fragile X Syndrome - genetics; Gene Library; Gene Rearrangement; Genetic Variation; Humans; Molecular Sequence Data; Nerve Tissue Proteins - genetics; Oligonucleotide Probes; Polymerase Chain Reaction - methods; Recombination, Genetic; Repetitive Sequences, Nucleic Acid; Restriction Mapping; RNA - genetics; RNA - isolation & purification; RNA-Binding Proteins; Translocation, Genetic; X Chromosome
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(91)90397-H

Fragile X syndrome Is the most frequent form of inherited mental retardation and Is associated with a fragile site at Xg27.3. We identified human YAC clones that span fragile X site-induced translocation breakpoints coincident with the fragile X site. A gene (FMR-1) was identified within 8 four cosmid contig of YAC DNA that expresses a 4.8 kb message in human brain. Within a 7.4 kb EcoFII genomic fragment, containing FMR-1 exonic sequences distal to a CpG island previously shown to be hypermethylated in fragile X patients, is a fragile X site-induced breakpoint cluster region that exhibits length variation in fragile X chromosomes. This fragment contains a lengthy CGG repeat that is 250 by distal of the CpG island and maps within a FMR-1 axon. Localization of the brain-expressed FMR-1 gene to this EcoRl fragment suggests the involvement of this gene in the phenotypic expression of the fragile X syndrome.