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Amalia C. Bruni, MD; Junko Takahashi-Fujigasaki, MD; Francesca Maltecca, PhD; Jean Francois Foncin, MD; Antonio Servadio, PhD; Giorgio Casari, PhD; Pio D’Adamo, PhD; Raffaele Maletta, MD; Sabrina A. M. Curcio, PhD; Giuseppe De Michele, MD; Alessandro Filla, MD; Khalid H. El Hachimi, PhD; Charles Duyckaerts, MD

Arch Neurol. 2004;61:1314-1320.

Background  Spinocerebellar ataxia type 17 is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in the TATA box-binding protein gene. Ataxia is typically the first sign whereas behavioral symptoms occur later.

Objective  To characterize the unusual phenotypic expression of a large spinocerebellar ataxia type 17 kindred.

Design  Clinical, neuropathological, and molecular genetic characterization of a 4-generation family with 16 affected patients.

Results  Behavioral symptoms and frontal impairment dominated the early stages preceding ataxia, rigidity, and dystonic movements. Neuropathological examination showed cortical, subcortical, and cerebellar atrophy. Purkinje cell loss and gliosis, pseudohypertrophic degeneration of the inferior olive, marked neuronal loss and gliosis in the caudate nucleus, and in the medial thalamic nuclei were salient features together with neuronal intranuclear inclusions stained with anti–TATA box-binding protein and antipolyglutamine antibodies. The disease was caused by a stable 52 CAG repeat expansion of the TATA box-binding protein gene, although there was apparent variability in the age of onset.

Conclusion  The characteristics of this family broaden the clinical picture of spinocerebellar ataxia type 17: initial presenile dementia with behavioral symptoms should be added to ataxia, rigidity, and dystonic movements, which are more commonly encountered.

Author Affiliations: Regional Neurogenetic Center AS6, Lamezia Terme (Drs Bruni, Maletta, and Curcio), San Raffaele Scientific Institute, DIBIT, Milano (Drs Maltecca, Servadio, and Casari), Telethon Institute of Genetics and Medicine, Napoli (Dr D’Adamo), Department of Neurological Sciences, University of Federico II, Napoli (Drs De Michele and Filla), Italy; Laboratoire de Neuropathologie Escourolle, La Salpêtrière (Drs Takahashi-Fujigasaki and Duyckaerts), INSERM U106, La Salpêtrière (Drs Takahashi-Fujigasaki, El Hachimi, and Duyckaerts), École Pratique des Hautes Études (Drs Foncin and El Hachimi), Paris, France.
Drs Maltecca and Servadio are currently with the Department of Experimental Environmental Medicine and Medical Biotechnologies, University of Milano-Bicocca, Monza, Italy.

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