Behavioral disorder, dementia, ataxia, and rigidity in a large family with TATA box-binding protein mutation.
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.


METHODS
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.


CONCLUSIONS
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.
Regional Neurogenetic Center AS6, Lamezia Terme, Italy. bruni@arn.it
Amalia C
AC
Bruni
Junko
J
Takahashi-Fujigasaki
Francesca
F
Maltecca
Jean Francois
JF
Foncin
Antonio
A
Servadio
Giorgio
G
Casari
Pio
P
D'Adamo
Raffaele
R
Maletta
Sabrina A M
SA
Curcio
Giuseppe
G
De Michele
Alessandro
A
Filla
Khalid H
KH
El Hachimi
Charles
C
Duyckaerts
D000328:Adult; D000368:Aged; D001526:Behavioral Symptoms / Q000235:genetics / Q000473:pathology / Q000523:psychology; D001921:Brain / Q000473:pathology; D003704:Dementia / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009127:Muscle Rigidity / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D009154:Mutation; D010375:Pedigree; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D035181:TATA-Box Binding Protein / Q000235:genetics*
D035181:TATA-Box Binding Protein