Intranuclear inclusions in a fragile X mosaic male

Translational Neurodegeneration

Flora Tassone⁶  Paul J Hagerman³  Deborah A Hall⁵  Stephen C Noctor¹  Randi J Hagerman²  Claudia M Greco¹  Christopher L Cunningham⁴  Michael R Hunsaker⁶  Dalyir I Pretto³ 

[1] Department of Pathology, School of Medicine, University of California at Davis, Davis, CA, USA;Department of Pediatrics, School of Medicine, University of California at Davis, Davis, CA, USA;Department of Biochemistry and Molecular Medicine, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA, USA;Neuroscience Graduate Program, University of California, Davis, Davis, CA, USA;Department of Biochemistry, Neurological Sciences, Rush University, Chicago, IL, USA;MIND Institute, University of California Davis Medical Center, Sacramento, CA, USA

关键词: Premutation;    FXTAS;    FXS;    Intranuclear inclusions;   

Others  :  838708
DOI  :  10.1186/2047-9158-2-10

 received in 2013-02-13, accepted in 2013-05-17,  发布年份 2013

【 摘 要 】

Lack of the fragile X mental retardation protein leads to Fragile X syndrome (FXS) while increased levels of FMR1 mRNA, as those observed in premutation carriers can lead to Fragile X- associated tremor ataxia syndrome (FXTAS). Until recently, FXTAS had been observed only in carriers of an FMR1 premutation (55–200 CGG repeats); however the disorder has now been described in individuals carriers of an intermediate allele (45–54 CGG repeats) as well as in a subject with a full mutation with mosaicism.

Here, we report on molecular and clinical data of a male FMR1 mosaic individual with full and premutation alleles. Molecular analysis of FMR1 and FMRP expression in this subject is consistent with a FXS phenotype. We observed reduced expression of FMRP in both peripheral blood and brain leading to the FXS diagnosis. In addition, a dramatic 90% depletion of both FMR1 mRNA and FMRP levels was observed in the blood, as normally observed in FXS cases, and an even greater depletion in the brain. A clinical report of this patient, at age 71, described neurodegenerative signs of parkinsonism that were likely, in retrospect, part of a FXTAS scenario as post-mortem examination shows the presence of intranuclear inclusions, the hallmark pathology of FXTAS.

The findings presented in this study indicate co-morbidity for both FXS and FXTAS in this individual carrying both full and premutation FMR1 alleles. In addition, based on symptoms and pathological and molecular evidence, this report suggests the need to redefine the diagnostic criteria of FXTAS.

【 授权许可】

   
2013 Pretto et al.; licensee BioMed Central Ltd.

【 图 表 】

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