Spinocerebellar ataxia type 17 (SCA17): oculomotor phenotype and clinical characterization of 15 Italian patients.
SCA17 is a rare type of autosomal dominant spinocerebellar ataxia caused by a CAG/CAA expansion in the gene encoding the TATA-binding protein (TBP). We screened for triplet expansion in the TBP gene 110 subjects with progressive cerebellar ataxia and 94 subjects with Huntington-like phenotype negative at specific molecular tests. SCA17 mutation-positive subjects were found in both groups of patients. Expanded alleles with > or = 44 CAG/CAA repeats were identified in 11 individuals and in 4 non-symptomatic relatives. Eleven de novo diagnosed patients and four patients previously reported underwent extensive clinical, neuroradiological and oculographic examination. Cerebellar signs and symptoms were present in all cases; 80% of the patients had mild to severe cognitive deficits; 66% of patients showed choreic movements; pyramidal signs, bradykinesia and dystonia were observed in approx 50% of the cases. MRI demonstrated cortical and cerebellar atrophy in all patients, whereas neurophysiological examination excluded signs of peripheral nervous system involvement. Oculographic examinations were performed in 9 out of 15 patients and showed a distinct pattern of oculomotor abnormalities, characterized by impairment of smooth pursuit, defects in the saccade accuracy, normal saccade velocity, hyperreflexia of vestibuloocular reflexes, and absence of nystagmus. In summary, this study presents one of the largest series of SCA17 patients in Europe. In our group of patients, SCA17 represents the third most frequent SCA genotype. Our clinical data confirm the large variability in SCA17 phenotypic presentation, and indicate that a peculiar combination of neuroradiological, electrophysiological and oculomotor findings is recognizable in SCA17.
Mariotti
Caterina
C
Division of Biochemistry and Genetics, Fondazione IRCCS - Istituto Neurologico, C. Besta, Milan, Italy.
Alpini
Dario
D
Fancellu
Roberto
R
Soliveri
Paola
P
Grisoli
Marina
M
Ravaglia
Sabrina
S
Lovati
Carlo
C
Fetoni
Vincenza
V
Giaccone
Giorgio
G
Castucci
Alessia
A
Taroni
Franco
F
Gellera
Cinzia
C
Di Donato
Stefano
S
D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009760:Nystagmus, Physiologic / Q000502:physiology; D015835:Ocular Motility Disorders / Q000209:etiology* / Q000473:pathology; D010641:Phenotype; D012027:Reflex, Vestibulo-Ocular / Q000235:genetics / Q000502:physiology; D020754:Spinocerebellar Ataxias / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D035181:TATA-Box Binding Protein / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion
D035181:TATA-Box Binding Protein; C509817:TBP protein, human