title: A genetic study of the FMR1 gene in a Sardinian multiple sclerosis population.
abstract: Multiple sclerosis (MS) is a complex autoimmune disease originated from the interplay between genetic and environmental factors. An overlap of clinical and neuroradiological parameters has been described between MS and an adult-onset neurodegenerative disorder, the fragile-X-associated tremor/ataxia syndrome (FXTAS). This syndrome is caused by a trinucleotide premutation expansion of a CGG sequence in the 55-200 repeat range, which is located in the fragile-X mental retardation 1 (FMR1) gene. Female premutation carriers have an increased propensity for immune-mediated disorders. Recently, a case of co-occurrence of MS and FXTAS was reported. Assuming that the premutation expansion may play a role in the MS susceptibility, we evaluated its frequency in a cohort of MS patients from Sardinia, an island characterized by a very high frequency of MS. Nuclear DNA was extracted by standard methods, purified with bisulfite treatment and then amplified twice by PCR with specific primers. Microsatellite analysis was performed and emizogotic subjects were sequenced. Clinical data of patients were also collected. Only 1/755 MS patients exhibited the premutation expansion with a heterozygosis pattern (30/58). No pathogenic repeat expansions (>200 repeats) were found in the entire cohort. Repeats labeled as the gray zone (45-60 repeats) were observed in 15/755 patients. No specific clinical features concerning disease course, disease activity, and disability were reported for these patients. Our results do not support a possible role for premutation or gray zone alleles in MS Sardinian patients. Further studies are needed to better understand the relationship between FXTAS and MS.
authors.affiliation: Department of Public Health and Clinical and Molecular Medicine, Multiple Sclerosis Center, University of Cagliari, Ospedale "Binaghi", via Is Guadazzonis, 2, 09126, Cagliari, Italy. lorena.lorefice@hotmail.it.
authors.forename: L
authors.initials: L
authors.lastname: Lorefice
authors.affiliation: Department of Medical Sciences, Institute of Neurology, University of Cagliari, Cagliari, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Tranquilli
authors.affiliation: Department of Public Health and Clinical and Molecular Medicine, Multiple Sclerosis Center, University of Cagliari, Ospedale "Binaghi", via Is Guadazzonis, 2, 09126, Cagliari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Fenu
authors.affiliation: ASL8-Department of Medical Sciences, Multiple Sclerosis Center, University of Cagliari, Cagliari, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Murru
authors.affiliation: Department of Public Health and Clinical and Molecular Medicine, Multiple Sclerosis Center, University of Cagliari, Ospedale "Binaghi", via Is Guadazzonis, 2, 09126, Cagliari, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Frau
authors.affiliation: ASL8-Department of Medical Sciences, Multiple Sclerosis Center, University of Cagliari, Cagliari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rolesu
authors.affiliation: Department of Public Health and Clinical and Molecular Medicine, Multiple Sclerosis Center, University of Cagliari, Ospedale "Binaghi", via Is Guadazzonis, 2, 09126, Cagliari, Italy.
authors.forename: G C
authors.initials: GC
authors.lastname: Coghe
authors.affiliation: Department of Medical Sciences, Institute of Neurology, University of Cagliari, Cagliari, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Marrosu
authors.affiliation: Department of Medical Sciences, Multiple Sclerosis Center, University of Cagliari, Cagliari, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Marrosu
authors.affiliation: Department of Public Health and Clinical and Molecular Medicine, Multiple Sclerosis Center, University of Cagliari, Ospedale "Binaghi", via Is Guadazzonis, 2, 09126, Cagliari, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cocco
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001259:Ataxia / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D014202:Tremor / Q000175:diagnosis / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: FMR1 gene; Fragile-X-associated tremor/ataxia syndrome; Gray zone alleles; Multiple sclerosis; Premutation; Sardinian population