Atypical Huntington's disease with the clinical presentation of behavioural variant of frontotemporal dementia.
Huntington's disease is an incurable, adult-onset, autosomal dominant inherited disorder caused by an expanded trinucleotide repeat (CAG). In this study, we describe a Huntington's disease patient displaying clinical symptoms of the behavioural variant of frontotemporal dementia in the absence of tremor and ataxia. The clinical onset was at the age of 36 years and the disease progressed slowly (18 years). Genetic testing revealed expanded trinucleotide CAG repeats in the Huntingtin gene, together with a Glu318Gly polymorphism in presenilin 1. Neuropathological assessment revealed extensive amyloid β (Aβ) aggregates in all cortical regions. No inclusions displaying hyperphosphorylated tau or phosphorylated transactive response DNA-binding protein 43 (TDP43) were found. A high number of p62 (sequestosome 1) immunopositive intranuclear inclusions were seen mainly in the cortex, while subcortical areas were affected to a lesser extent. Confocal microscopy revealed that the majority of p62 intranuclear lesions co-localised with the fused-in-sarcoma protein (FUS) immunostaining. The morphology of the inclusions resembled intranuclear aggregates in Huntington's disease. The presented proband suffered from Huntington's disease showed atypical distribution of FUS positive intranuclear aggregates in the cortical areas with concomitant Alzheimer's disease pathology.
Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
Stanislav
S
Sutovsky
Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska 9, 845 10, Bratislava, Slovak Republic.
Tomas
T
Smolek
Department of Immunology, Genetics and Pathology, Department of Clinical Pathology, Uppsala University Hospital, Uppsala University, Uppsala, Sweden.
Irina
I
Alafuzoff
Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
Andrej
A
Blaho
Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska 9, 845 10, Bratislava, Slovak Republic.|Institute of Neuroimmunology, n.o., Bratislava, Slovak Republic.
Vojtech
V
Parrak
Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
Peter
P
Turcani
Department of Pathological Anatomy, Commenius University, Bratislava, Slovak Republic.
Michal
M
Palkovic
Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Commenius University, Bratislava, Slovak Republic.
Robert
R
Petrovic
Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska 9, 845 10, Bratislava, Slovak Republic.
Michal
M
Novak
Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska 9, 845 10, Bratislava, Slovak Republic. norbert.zilka@savba.sk.|Institute of Neuroimmunology, n.o., Bratislava, Slovak Republic. norbert.zilka@savba.sk.
Norbert
N
Zilka
D000328:Adult; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005192:Family Health; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications*; D000072473:Fused-Ring Compounds / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics; D006816:Huntington Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
D016229:Amyloid beta-Peptides; D000072473:Fused-Ring Compounds; D000071058:Huntingtin Protein; C118585:P62 protein, human; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016601:RNA-Binding Proteins
Amyloid; Behavioural variant FTD; FUS; Huntingtin; Intranuclear inclusions