title: A microdeletion of less than 250 kb, including the proximal part of the FMR-I gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome.
abstract: A gene designated "FMR-1" has been isolated at the fragile-X locus. One exon of this gene is carried on a 5.1-kb EcoRI fragment that exhibits length variation in fragile-X patients because of amplification of or insertion into a CGG-repeat sequence. This repeat probably represents the fragile site. The EcoRI fragment also includes an HTF island that is hypermethylated in fragile-X patients showing absence of FMR-1 mRNA. In this paper, we present further evidence that the FMR-1 gene is involved in the clinical manifestation of the fragile-X syndrome and also in the expression of the cellular phenotype. A deletion including the HTF island and exons of the FMR-1 gene was detected in a fragile X-negative mentally retarded male who presented the clinical phenotype of the fragile-X syndrome. The deletion involves less than 250 kb of genomic DNA, including DXS548 and at least five exons of the FMR-1 gene. These data support the hypothesis that loss of function of the FMR-1 gene leads to the clinical phenotype of the fragile-X syndrome. In the fragile-X syndrome, there are pathogenetic mechanisms other than amplification of the CGG repeat that do have the same phenotypic consequences.
authors.affiliation: Abteilung Klinische Genetik, Universität Ulm, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Wöhrle
authors.forename: D
authors.initials: D
authors.lastname: Kotzot
authors.forename: M C
authors.initials: MC
authors.lastname: Hirst
authors.forename: A
authors.initials: A
authors.lastname: Manca
authors.forename: B
authors.initials: B
authors.lastname: Korn
authors.forename: A
authors.initials: A
authors.lastname: Schmidt
authors.forename: G
authors.initials: G
authors.lastname: Barbi
authors.forename: H D
authors.initials: HD
authors.lastname: Rott
authors.forename: A
authors.initials: A
authors.lastname: Poustka
authors.forename: K E
authors.initials: KE
authors.lastname: Davies
mesh_terms: D001483:Base Sequence; D002648:Child; D002872:Chromosome Deletion; D004247:DNA; D015342:DNA Probes; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins; D015183:Restriction Mapping
chemical_list: D004247:DNA; D015342:DNA Probes; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human