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Molecular Inconsistencies in a Fragile X Male with Early Onset Ataxia

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....

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Autores principales: Hwang, Yun Tae, Dudding, Tracy, Aliaga, Solange Mabel, Arpone, Marta, Francis, David, Li, Xin, Slater, Howard Robert, Rogers, Carolyn, Bretherton, Lesley, du Sart, Desirée, Heard, Robert, Godler, David Eugeny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042398/
https://www.ncbi.nlm.nih.gov/pubmed/27657133
http://dx.doi.org/10.3390/genes7090068
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author Hwang, Yun Tae
Dudding, Tracy
Aliaga, Solange Mabel
Arpone, Marta
Francis, David
Li, Xin
Slater, Howard Robert
Rogers, Carolyn
Bretherton, Lesley
du Sart, Desirée
Heard, Robert
Godler, David Eugeny
author_facet Hwang, Yun Tae
Dudding, Tracy
Aliaga, Solange Mabel
Arpone, Marta
Francis, David
Li, Xin
Slater, Howard Robert
Rogers, Carolyn
Bretherton, Lesley
du Sart, Desirée
Heard, Robert
Godler, David Eugeny
author_sort Hwang, Yun Tae
collection PubMed
description 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.
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spelling pubmed-50423982016-09-29 Molecular Inconsistencies in a Fragile X Male with Early Onset Ataxia Hwang, Yun Tae Dudding, Tracy Aliaga, Solange Mabel Arpone, Marta Francis, David Li, Xin Slater, Howard Robert Rogers, Carolyn Bretherton, Lesley du Sart, Desirée Heard, Robert Godler, David Eugeny Genes (Basel) Case Report 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. MDPI 2016-09-21 /pmc/articles/PMC5042398/ /pubmed/27657133 http://dx.doi.org/10.3390/genes7090068 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Hwang, Yun Tae
Dudding, Tracy
Aliaga, Solange Mabel
Arpone, Marta
Francis, David
Li, Xin
Slater, Howard Robert
Rogers, Carolyn
Bretherton, Lesley
du Sart, Desirée
Heard, Robert
Godler, David Eugeny
Molecular Inconsistencies in a Fragile X Male with Early Onset Ataxia
title Molecular Inconsistencies in a Fragile X Male with Early Onset Ataxia
title_full Molecular Inconsistencies in a Fragile X Male with Early Onset Ataxia
title_fullStr Molecular Inconsistencies in a Fragile X Male with Early Onset Ataxia
title_full_unstemmed Molecular Inconsistencies in a Fragile X Male with Early Onset Ataxia
title_short Molecular Inconsistencies in a Fragile X Male with Early Onset Ataxia
title_sort molecular inconsistencies in a fragile x male with early onset ataxia
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042398/
https://www.ncbi.nlm.nih.gov/pubmed/27657133
http://dx.doi.org/10.3390/genes7090068
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