Spinocerebellar ataxia 48 presenting with ataxia associated with cognitive, psychiatric, and extrapyramidal features: A report of two Italian families(40 visite) De Michele G, Lieto M, Galatolo D, Salvatore E, Cocozza S, Barghigiani M, Tessa A, Baldacci J, Pappata S, Filla A, De Michele G, Santorelli FM
Parkinsonism Relat Disord (ISSN: 1353-8020linking), 2019 May 14; 65: 91-96.
Tipo di articolo: Journal Article
Impact factor: 4.721, Impact factor a 5 anni: 3.173
Url: Non disponibile.
Parole chiave: Ataxia, Chip, Dominant, Hd-Like, Sca48, Stub1
*** IBB - CNR *** Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy. IRCCS Fondazione Stella Maris, Pisa, Italy. Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. Biostructure and Bioimaging Institute, CNR, Naples, Italy.
INTRODUCTION: Spinocerebellar ataxia 48 has recently been described as an adult onset ataxia associated with a cerebellar cognitive affective syndrome, caused by a heterozygous mutation in the STUB1 gene. METHODS: We characterized the clinical and neuroimaging phenotype of eight patients from two autosomal dominant ataxia multigenerational Italian families, in whom we conducted whole exome sequencing, targeted multigene sequencing, and Sanger sequencing studies. RESULTS: We describe a complex syndrome characterized by ataxia and cognitive-psychiatric disorder in all cases, variably associated with chorea, parkinsonism, dystonia, urinary symptoms, and epilepsy. MRI showed a significant cerebellar atrophy, coupled to a T2-weighted hyperintensity affecting the dentate nuclei and extending to the middle cerebellar peduncles, whereas FDG-PET studies revealed glucose hypometabolism in cerebellum, striatum, and cerebral cortex. We identified two different novel STUB1 mutations segregating in the two families. One of the two mutations, p.(Gly33Ser), occurs in the TRP domain, whereas p.(Pro228Ser) is located in the ubiquitin ligase region. DISCUSSION: We emphasize the similarity of the described clinical picture with that of SCAR16, an autosomal recessive ataxia caused by biallelic mutations in the same gene, and of spinocerebellar ataxia type 17, which is considered the main Huntington's disease-like syndrome. The pathogenesis of the disease and the relationship between SCA48 and SCAR16 remain to be clarified.<br>
10 Records (10 escludendo Abstract e Conferenze). Impact factor totale: 36.696 (36.696 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 38.445 (38.445 escludendo Abstract e Conferenze).