title: The -413C > G substitution in the promoter of the FMR1 gene is not associated with the fragile X syndrome phenotype.
abstract: Most common inherited form of intellectual disability, fragile X syndrome is associated to an expansion of greater than 200 CGG repeats in the 5' untranslated region of the FMR1 gene on the X chromosome which causes transcriptional silencing and deficiency of the encoded protein FMRP. Molecular diagnosis is performed through a combination of PCR to identify fewer than 100-150 repeats and of Southern blot analysis to identify longer alleles and the methylation status of the FMR1 promoter. We present a family with one patient with mild mental retardation who showed an atypical profile at Southern analysis due to the -413C > G transversion located in the FMR1 promoter which had been described as possibly associated with mental retardation. We demonstrated this variant in other four family members along three generations, including the maternal grandfather who did not manifest any pathological feature. Though the -413C > G substitution was not found in a large control series, these findings allowed to exclude its role in determining the disease phenotype.
authors.affiliation: Laboratory of Genetics, Galliera Hospital, Via Volta 6, 16128 Genova, Italy. marina.grasso@galliera.it <marina.grasso@galliera.it>
authors.forename: Marina
authors.initials: M
authors.lastname: Grasso
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cecconi
authors.forename: Stefania
authors.initials: S
authors.lastname: Boni
authors.forename: Francesca
authors.initials: F
authors.lastname: Forzano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Barbaresi
authors.forename: Luigi
authors.initials: L
authors.lastname: Memo
authors.forename: Lucia
authors.initials: L
authors.lastname: Perroni
authors.forename: Francesca
authors.initials: F
authors.lastname: Faravelli
authors.forename: Emilio
authors.initials: E
authors.lastname: Di Maria
mesh_terms: D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1