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. 2020 Oct 15;36(2):508–514. doi: 10.1002/mds.28334

FIG. 2.

FIG. 2

Clinical information, genetics, and neuropathology of Swedish SCA3 parkinsonian family with both intermediate CAG repeats and novel 9‐bp duplication. (A) Pedigree of the SCA3 family with the 9‐bp duplication. (B) Genotype and phenotype of individuals involved in this familiar study. (C) Neuropathology of case I‐1, indicating moderate loss of pigmented neurons in the substantia nigra and also being positive for ubiquitin and p62. (D) Three arrows indicate 3 ubiquitin‐positive intranuclear inclusions in a pigmented neuron in the substantia nigra. (E) Numerous neurons in the pons contained intranuclear polyQ‐positive inclusions. (F) Some loss of Purkinje cells in the cerebellar cortex was noticed. (G) CT scan for the index case. (H) [123I]FP‐CIT SPECT in patient II‐1 displaying significantly reduced binding to dopamine transporter. (I) [123I] FP‐CIT SPECT image from a healthy control. (J) Generalized estimated equation analysis of the AO‐CAG relationship in the Swedish cohort highlighting individuals I‐1 (father) and II‐1 (daughter). Red curve is for the full SCA3 cohort, blue curve is when excluding the 9‐bp duplication carrier (II‐1), and black is when both the 9‐bp duplication carrier (II‐1) and I‐1 with an intermediate ATXN2 CAG are excluded. Model effects are presented in the inset box. The index case II‐1 deviates from the expected AO, as shown in the residual analysis in (K) and in different models (Table S4). (L) The same effect of lowering disease onset is also found in the 2 C9ORF72‐ALS cases carrying the 9‐bp duplication. In the box‐and‐whiskers plots, there are 3 groups: ALS with C9ORF72 mutation only (C9), ALS with C9ORF72 plus intermediate ATXN2 CAG (ATXN2), and the 2 C9ORF72‐ALS carriers with the 9‐bp duplication (DUP). Box‐and‐whisker plots represent median and the 25%–75% interquartile range as well as the 5th–95th percentiles. Note that there is no overlap between the ATXN2 and DUP groups. Purple points represent values outside the 5th–95th percentiles. [Color figure can be viewed at wileyonlinelibrary.com]