title: FXTAS in an unmethylated mosaic male with fragile X syndrome from Chile.
abstract: Carriers of an FMR1 premutation allele (55-200 CGG repeats) often develop the neurodegenerative disorders, fragile X-associated tremor/ataxia syndrome (FXTAS). Neurological signs of FXTAS, parkinsonism and rapid onset of cognitive decline have not been reported in individuals with an unmethylated full mutation (FM). Here, we report a Chilean family affected with FXS, inherited from a parent carrier of an FMR1 unmethylated full mosaic allele, who presented with a fast progressing FXTAS. This case suggests that the definition of FXTAS may need to be broadened to not only include those with a premutation but also those with an expanded allele in FM range with a lack of methylation leading to elevated FMR1-mRNA expression levels and subsequent RNA toxicity.
authors.affiliation: Center for Diagnosis and Treatment of Fragile X Syndrome (CDTSXF), INTA University of Chile, Santiago, Chile.
authors.forename: L
authors.initials: L
authors.lastname: Santa María
authors.forename: A
authors.initials: A
authors.lastname: Pugin
authors.forename: M A
authors.initials: MA
authors.lastname: Alliende
authors.forename: S
authors.initials: S
authors.lastname: Aliaga
authors.forename: B
authors.initials: B
authors.lastname: Curotto
authors.forename: T
authors.initials: T
authors.lastname: Aravena
authors.forename: H-T
authors.initials: HT
authors.lastname: Tang
authors.forename: G
authors.initials: G
authors.lastname: Mendoza-Morales
authors.forename: R
authors.initials: R
authors.lastname: Hagerman
authors.forename: F
authors.initials: F
authors.lastname: Tassone
mesh_terms: D000368:Aged; D001259:Ataxia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002677:Chile; D019175:DNA Methylation / Q000235:genetics*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D009030:Mosaicism; D014202:Tremor / Q000150:complications / Q000235:genetics* / Q000473:pathology
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: FXTAS; fragile X; parkinsonism; unmethylated full mutation
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2007 Jun 5;144B(4):566-9
references.pmid: 17427188
references.citation: Transl Neurodegener. 2013 May 21;2(1):10
references.pmid: 23692864
references.citation: J Clin Psychiatry. 2009 Jun;70(6):852-62
references.pmid: 19422761
references.citation: Am J Med Genet. 2000 Sep 18;94(3):232-6
references.pmid: 10995510
references.citation: Brain. 2002 Aug;125(Pt 8):1760-71
references.pmid: 12135967
references.citation: Genome Med. 2012 Dec 21;4(12):100
references.pmid: 23259642
references.citation: Clin Genet. 2012 Jul;82(1):88-92
references.pmid: 21476992
references.citation: AJNR Am J Neuroradiol. 2002 Nov-Dec;23(10):1757-66
references.pmid: 12427636
references.citation: J Hum Genet. 2010 Jan;55(1):66-8
references.pmid: 19927162
references.citation: Behav Genet. 2005 Jul;35(4):435-45
references.pmid: 15971024
references.citation: Lancet Neurol. 2013 Aug;12(8):786-98
references.pmid: 23867198
references.citation: Mov Disord. 2006 Jan;21(1):98-102
references.pmid: 16124012
references.citation: Am J Hum Genet. 2000 Jan;66(1):6-15
references.pmid: 10631132
references.citation: J Mol Diagn. 2008 Jan;10(1):43-9
references.pmid: 18165273
references.citation: Exp Cell Res. 2007 Jan 15;313(2):244-53
references.pmid: 17150213
references.citation: Arq Neuropsiquiatr. 2010 Oct;68(5):791-8
references.pmid: 21049196
references.citation: Hum Mol Genet. 2011 Jun 1;20(11):2161-70
references.pmid: 21389081
references.citation: J Neuropathol Exp Neurol. 2011 Jun;70(6):462-9
references.pmid: 21572337
references.citation: J Mol Diagn. 2009 Jul;11(4):281-9
references.pmid: 19460937
references.citation: Am J Hum Genet. 2003 Apr;72(4):869-78
references.pmid: 12638084
references.citation: Clin Genet. 2013 Jul;84(1):74-7
references.pmid: 23009394
references.citation: Cell. 1991 May 31;65(5):905-14
references.pmid: 1710175
references.citation: Mov Disord. 2007 Jan 15;22(2):203-6
references.pmid: 17133502
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Oct 5;147B(7):1138-44
references.pmid: 18384046
references.citation: Clin Chem. 2010 Mar;56(3):399-408
references.pmid: 20056738
references.citation: Mov Disord. 2012 Feb;27(2):296-300
references.pmid: 22161987