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Erratum published on 24 January 2017, see Genes 2017, 8(2), 47.

Open AccessCase Report
Genes 2016, 7(9), 68; doi:10.3390/genes7090068

Molecular Inconsistencies in a Fragile X Male with Early Onset Ataxia

1
Department of Neurology, Gosford Hospital, Gosford 2250, Australia
2
Institute of Neurology, University College London, London WC1N 3BG, UK
3
Genetics of Learning Disability Service, Hunger Genetics, Waratah 2298, Australia
4
Grow Up Well Priority Research Centre, University of Newcastle, Waratah 2308, Australia
5
Cyto-molecular Diagnostic Research Laboratory, Victorian Clinical Genetics Services and Murdoch Childrens Research Institute, Royal Children’s Hospital, Melbourne 3052, Australia
6
Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne 3010, Australia
7
Molecular and Cytogenetics Laboratory, INTA University of Chile, Santiago 7830490, Chile
8
Psychology Service, Royal Children’s Hospital, Melbourne 3052, Australia
9
Melbourne School of Psychological Sciences, University of Melbourne, Melbourne 3052, Australia
10
Child Neuropsychology, Murdoch Childrens Research Institute, Royal Children’s Hospital, Melbourne 3052, Australia
11
Molecular Genetics Laboratory, Victorian Clinical Genetics Services and Murdoch Childrens Research Institute, Royal Children’s Hospital, Melbourne 3052, Australia
12
Faculty of Medicine, University of Newcastle, Newcastle 2303, Australia
13
Westmead Millennium Institute, University of Sydney, Westmead 2145, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Mark Hirst
Received: 12 May 2016 / Revised: 22 August 2016 / Accepted: 13 September 2016 / Published: 21 September 2016
(This article belongs to the Special Issue Fragile X Syndrome)
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Abstract

Mosaicism for FMR1 premutation (PM: 55–199 CGG)/full mutation (FM: >200 CGG) alleles or the presence of unmethylated FM (UFM) have been associated with a less severe fragile X syndrome (FXS) phenotype and fragile X associated tremor/ataxia syndrome (FXTAS)—a late onset neurodegenerative disorder. We describe a 38 year old male carrying a 100% methylated FM detected with Southern blot (SB), which is consistent with complete silencing of FMR1 and a diagnosis of fragile X syndrome. However, his formal cognitive scores were not at the most severe end of the FXS phenotype and he displayed tremor and ataxic gait. With the association of UFM with FXTAS, we speculated that his ataxia might be related to an undetected proportion of UFM alleles. Such UFM alleles were confirmed by more sensitive PCR based methylation testing showing FM methylation between 60% and 70% in blood, buccal, and saliva samples and real-time PCR analysis showing incomplete silencing of FMR1. While he did not meet diagnostic criteria for FXTAS based on MRI findings, the underlying cause of his ataxia may be related to UFM alleles not detected by SB, and follow-up clinical and molecular assessment are justified if his symptoms worsen. View Full-Text
Keywords: fragile X syndrome; FMR1; FXTAS; ataxia; tremor; methylation; mosaicism; AmplideX; Southern blot; RNA toxicity fragile X syndrome; FMR1; FXTAS; ataxia; tremor; methylation; mosaicism; AmplideX; Southern blot; RNA toxicity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hwang, Y.T.; Dudding, T.; Aliaga, S.M.; Arpone, M.; Francis, D.; Li, X.; Slater, H.R.; Rogers, C.; Bretherton, L.; du Sart, D.; Heard, R.; Godler, D.E. Molecular Inconsistencies in a Fragile X Male with Early Onset Ataxia. Genes 2016, 7, 68.

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