Cerebellar cognitive-affective syndrome preceding ataxia associated with complex extrapyramidal features in a Turkish SCA48 family

Reply to letter to the editor by De Michele et al

“…De Michele et al's patient, and the single Turkish case. Our patient's clinical phenotype regarding the cognitive-affective aspect of c.823_824delCT-based SCA48 is fully consistent with the Genis' family, except for Genis' case VII-1, who belongs to the younger generation of the family and may not yet have manifested the full-blown disease [1,2]. De Michele et al's patient 10 presenting with pure cerebellar ataxia as an initial symptom, typical for SCAs, has overlapping symptoms with our patient, but these symptoms manifest in a different temporal profile [4].…”

“…We are grateful to De Michele et al for their enlightening and constructive comments on our study on c.823_824delCTbased SCA48, which seems to be a recurrent dominant ataxia in the Mediterranean Basin; we have just identified another Turkish patient with SCA48, although with a different STUB1 variant [1,2].…”

Clinical and pathologic phenotype of a large family with heterozygous STUB1 mutation

“…Chorea or uncontrolled motor activity was frequently reported, showing resemblance with the chorea described in several other families. [10][11][12] Parkinsonism was also present in 4 of 11 described Italian patients with SCA48. 11 Atypical parkinsonism with features resembling PSP was observed in 1 patient.…”

“…Other published SCA48 pedigrees with mutations in close proximity to the current mutation showed a broad range of cognitive symptoms. [9][10][11][12] Another interesting observation is the presence of other movement disorders besides gait ataxia. Chorea or uncontrolled motor activity was frequently reported, showing resemblance with the chorea described in several other families.…”

“…7,8 More recently, heterozygous variants in STUB1 have been implicated in autosomal dominant SCA (SCA48; OMIM#618093), characterized by a complex phenotype including cognitive/ affective symptoms and movement disorders. [9][10][11][12] In this study, we present a large Dutch SCA48 family associated with a novel heterozygous frameshift mutation in the U-box domain of STUB1 and describe the neuropathologic features of 3 patients in this family.…”