Journal Article

FZJ-2021-01213

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Spinocerebellar ataxia type 14: Refining clinico-genetic diagnosis in a rare adult-onset disorder

Schmitz-Hübsch, T. (Corresponding author) ; Lux, S. ; Bauer, P. ; Brandt, A. U. ; Schlapakow, E. ; Greschus, S. ; Scheel, M. ; Gärtner, H. ; Kirlangic, M. E. ; Gras, V. ; Timmann, D. ; Synofzik, M. ; Giorgetti, A.FZJ* ; Carloni, P.FZJ* ; Shah, N. J.FZJ* ; Schöls, L. ; Kopp, U. ; Bußenius, L. ; Oberwahrenbrock, T. ; Zimmermann, H. ; Pfueller, C. ; Kadas, E. M. ; Rönnefarth, M. ; Grosch, A. S. ; Endres, M. ; Amunts, K.FZJ* ; Friedemann, P. ; Doss, S. ; Minnerop, M. (Corresponding author)FZJ*

2021
Wiley Chichester [u.a.]

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Please use a persistent id in citations: http://hdl.handle.net/2128/27752  doi:10.1002/acn3.51315

Abstract: ObjectivesGenetic variant classification is a challenge in rare adult‐onset disorders as in SCA‐PRKCG (prior spinocerebellar ataxia type 14) with mostly private conventional mutations and nonspecific phenotype. We here propose a refined approach for clinicogenetic diagnosis by including protein modeling and provide for confirmed SCA‐PRKCG a comprehensive phenotype description from a German multi‐center cohort, including standardized 3D MR imaging.MethodsThis cross‐sectional study prospectively obtained neurological, neuropsychological, and brain imaging data in 33 PRKCG variant carriers. Protein modeling was added as a classification criterion in variants of uncertain significance (VUS).ResultsOur sample included 25 cases confirmed as SCA‐PRKCG (14 variants, thereof seven novel variants) and eight carriers of variants assigned as VUS (four variants) or benign/likely benign (two variants). Phenotype in SCA‐PRKCG included slowly progressive ataxia (onset at 4–50 years), preceded in some by early‐onset nonprogressive symptoms. Ataxia was often combined with action myoclonus, dystonia, or mild cognitive‐affective disturbance. Inspection of brain MRI revealed nonprogressive cerebellar atrophy. As a novel finding, a previously not described T2 hyperintense dentate nucleus was seen in all SCA‐PRKCG cases but in none of the controls.

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Contributing Institute(s):

1. Strukturelle und funktionelle Organisation des Gehirns (INM-1)
2. Computational Biomedicine (IAS-5)
3. Computational Biomedicine (INM-9)
4. Physik der Medizinischen Bildgebung (INM-4)
5. Jara-Institut Quantum Information (INM-11)
6. Jülich-Aachen Research Alliance - Translational Brain Medicine (JARA-BRAIN)

Research Program(s):

1. 525 - Decoding Brain Organization and Dysfunction (POF4-525) (POF4-525)

Appears in the scientific report 2021

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