Table 29.2.
Octapeptide repeat insertions and deletions
| PRNP mutation | Codon 129 polymorphism | # of cases in literature | Clinical phenotypes | Age at onset (range)c (years) | Disease duration (range)c (months or years) | Positive FHxa | CSF marker
sensitivity |
EEG PSWC | MRI c/w JCDb | Neuropathology | Neuropathology pheno-type | References | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 14-3-3 | Total taud | ||||||||||||
| 2-OPRD | MM (1) Unknown (1) | 2 | RPD RPD, Sz, Myo | (62–86) | (18–23) months | 0% (0/2) | N/A | N/A | N/A | N/A | JCD | Beck et al., (2001); Capellari et al. (2002) | |
| 2-OPRI | MM (1) MV (1) VV (1) Unknown (1) | 4 | RPD D Cbr Atx | Mean 63.3 ± 7.9 (58–75) | Mean 6.8 ± 6.4 (0.25–13) years | 50% (2/4) | N/A | N/A | N/A | 0% (0/1) | JCD | Goldfarbe et al. (1993); Croes et al. (2004); van Harten et al.(2000) | |
| 3-OPRI | VV (1) MM(1) | 2 | RPD | (68–69) | (4 months–3 years) | 0% (0/1) | 50% (1/2) | N/A | 50% (1/2) | 100% (1/1) | JCD | Grasbon-Frodl et al. (2004) ; Nishida et al.(2004) | |
| 4-OPRI | MM(9) VV (1) MV (Cis V, 1) | 11 | MM: RPD, Myo, Cbr, Atx VV: Dep, Behav MV: RPD | MM: Mean 60 ± 13.6 (39–85) VV: 82 MV: 38 | MM: mean 33.8 ± 32.7 (2–76) months VV: 4 months MV 8 months | MM: 12.5% (1/8) VV: 0% (0/1) MV: 100% (1/1) | MM: 100% (4/4) VV: N/A MV: 100% (1/1) | N/A | MM:22% (2/9) VV: 100% (1/1) MV: 0% (0/1) | MM: 20%(1/5) VV: N/A MV: 100% (1/1) | MM: JCD (7/7) VV: N/A MV: JCD (1/1) | Laplanche et al. (1995); Kaski et al. (2011); Sanchez-Valle et al. (2012) | |
| 5-OPRI | MM (6) MV (Cis M, 3) Unknown (8) | 17 | Cog, motor | Mean 45.7±11.0 (26–63), | Mean 76 ± 51.8 (10months–14.5 years) | 100% (15/15) | 100% (1/1) | N/A | 25%(2/8) | 0% (0/8) | V, Neu loss, kuru-like PrPSc | Goldfarb et al. (1991); Cochran et al. (1996); Skworc et al. (1999); Beck et al. (2005); Mead et al. (2007) | |
| 5-OPRI* | MM (1) | 1 | Visuosp | 39 | 19Y | FHx score 2 | N/A | N/A | 0% | 0% | N/A | Takada et al. (2017) | |
| 6-OPRI | 63 | Cog D, Front, Cbr Atx | MM (30) 31.4 MV (10) 41.7 | MM (19) 11.4Y, MV (8) 8.9Y | N/A | N/A | 0% | 0% | Mead et al. (2006) | ||||
| 6-OPRI* | Cis M (3) Cis V (2) | 5 | Cog, Cbr Atx | Cis M 35±2.6 (32–37) Cis V (47–51) | Cis M 5.9±3(3–9) years Cis V (5–10) months | FHx score 2(n = 5) | 0% (0/2) | 0% (0/2) | 0% (0/2) | 0% (0/5) | JCD (4/4) | Takada et al. (2017) | |
| 7-OPRI | Cis M/Cis V | 16 | Cog, Behav Motor | 35 ±12.4 (18–59) | 8.4 ±4.9, (0.6–17) | 86% (6/7) | N/A | N/A | 33.3% (1/3) | 50% (1/2) | Cis M no PrP-Plqs Cis V Uni-, multicentric PrP-Plqs | Goldfarb et al. (1991); Tateishi et al. (1991); Brown et al. (1992); Dermaut et al. (2000) Lewis et al. (2003); Cannella et al. (2007) Wang et al. (2007); Guo et al. (2008); Mauro et al. (2008); Jansen et al. (2011) | |
| 8-OPRI | Cis M (4) | 11 | Psy, D | Mean 28 (21–34) | Mean 3.8 (1–7) years | 100% (11/11) | N/A | N/A | 0% (0/3) | 0% (0/2) | Kuru, multicentric PrP-Plqs | GSS | Laplanche et al. (1999) |
| 8-OPRI* | MM | 1 | Dep, Cbr Atx | 22 | >5 yearse | FHx score 0 | N/A | N/A | N/A | 0% | N/A | Takada et al. (2017) | |
| 9-OPRI | Cis M (2) Unknown (1) | 3 | Cbr Atx Fall, Cog Behav, Cog | 47±13 (32–55) | (7 months–2.5 years) | N/A | N/A | N/A | 0% (0/1) | 0% (0/1) | Numerous small PrP plaqs | Owen et al. (1992); Duchen et al. (1993); Krasemann et al.(1995) | |
| 9-OPRI* | VV (1) | 1 | Visuosp, Cog | 47 | 21 months | FHx score 0 | N/A | 100% (1/1) | 100% (1/1) | 100% (1/1) | JCD+ GSS | Takada et al. (2017) | |
| 12-OPRI | N/A | 3 | Cog, Behav, Cbr Atx, Sz | 44 ± 1 (43–45) | 8±1.7 (7–10) | 100% (3/3) | 0% (0/1) | 100% (1/1) | 0% (0/1) | 0% (0/1) | Multicentric PrP-Plqs | GSS | Kumar et al. (2011) |
Positive family history of dementia with similar clinical features (as of the proband) or prion disease (PrD). For UCSF family history (FHx) score scale: 0 when there was no positive family medical history suspicious for or known PrD; 1 when there was at least one first-degree relative with dementia, encephalopathy, or movement disorder; or 2 in patients who were part of families with known PRNP mutations, or had positive history for clinical or path-proven PrDs.
According to most commonly used European 2009 and UCSF 2011 criteria (Zerr et al., 2009; Vitali et al., 2011).
Data on age at onset and duration of disease are shown as mean ± sd (range), unless otherwise indicated.
Positive if > total tau 1200 pg/mL.
Some patients still alive, so duration at last follow-up.
If there are differences between data published in the literature from the more recently published University of California, San Francisco (UCSF) cohort, this information is provided in the table separately for that mutation. Atx, ataxia; Cbr, cerebellar; c/w, consistent with; Behav, behavioral changes; Cog, cognitive; CSF, cerebrospinal fluid; D, dementia; Dep, depression; EEG, electroencephalogram; FHx, family history; Front, frontal-lobe dysfunction; GSS, Gerstmann–Sträussler–Scheinker; JCD, Jakob–Creutzfeldt disease; MRI, magnetic resonance imaging; Myo, myoclonus; N/A, not available; Neu, neuronal; OPRD, octapeptide repeat deletion; OPRI, octapeptide repeat insertion mutation; PrP-Plqs, PrP-amyloid plaques; PSWC, periodic sharp-wave complexes; Psy, psychiatric changes; RPD, rapidly progressive dementia; Sz, seizures; Visuosp, visuospatial.