Table 2.
Octapeptide repeat insertions and deletions
| PRNP mutation | Codon 129 polymorphism | Number of cases in literature | Clinical phenotypes | Age at onset (range)a (yr) | Disease duration (range)a (mo or yr) | Pos FHxb | CSF biomarker sensitivity | EEG PSWC | MRI c/w CJDd | Neuropathology | Neuropathologic phenotype | References | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 14-3-3 | Total tauc | ||||||||||||
| 2-OPRD | MM (1) Unknown (1) | 2 | RPD RPD, Sz, Myo |
(62–86) | (18–23) mo | 0% (0/2) | N/A | N/A | N/A | N/A | CJD | 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) yr | 50% (2/4) | N/A | N/A | N/A | 0% (0/1) | CJD | Goldfarb et al. 1993; van Harten et al. 2000; Croes et al. 2004 | |
| 3-OPRI | VV (1) MM (1) | 2 | RPD | (68–69) | (4 mo–3 yr) | 0% (0/1) | 50% (1/2) | N/A | 50% (1/2) | 100% (1/1) | CJD | 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) mo VV 4 mo MV 8 mo | MM 12.5% (1/8) VV 0% (0/1) MV 100% (1/1) | MM100% (4/4) VV N/A MV 100% (1/1) | N/A | MM22% (2/9) VV 100% (1/1) MV 0% (0/1) | MM 20% (1/5) VV N/A MV 100% (1/1) | MM CJD (7/7) VV N/A MV CJD (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 (10 mo–14.5 yr) | 100% (15/15) | 100% (1/1) | N/A | 25% (2/8) | 0% (0/8) | Vac, 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-OPRIe | MM (1) | 1 | Visuosp | 39 | 19 yr | 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) 11.4 yr, MV (8) 8.9 yr | N/A | N/A | 0% | 0% | Mead et al. 2006 | ||||
| 6-OPRIe | 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) yr Cis V (5–10) mo | FHx score 2 (n = 5) | 0% (0/2) | 0% (0/2) | 0% (0/2) | 0% (0/5) | CJD (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) yr | 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. 1992b; Dermaut et al. 2000; Lewis et al. 2003; Cannella et al. 2007; Mauro et al. 2008; Wang et al. 2007; Guo et al. 2008; Jansen et al. 2011 | |
| 8-OPRI | cis M (4) | 11 | Psy, D | Mean 28 (21–34) | Mean 3.8 (1–7) yr | 100% (11/11) | N/A | N/A | 0% (0/3) | 0% (0/2) | Kuru, multicentric PrP-Plqs | GSS | Laplanche et al. 1999 |
| 8-OPRIe | MM | 1 | Dep, Cbr Atx | 22 | >5 yrf | 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 mo–2.5 yr) | N/A | N/A | N/A | 0% (0/1) | 0% (0/1) | numerous small PrP Plqs | Owen et al. 1992; Duchen et al. 1993; Krasemann et al. 1995 | |
| 9-OPRIe | VV (1) | 1 | Visuosp, Cog | 47 | 21 mo | FHx score 0 | N/A | 100% (1/1) | 100% (1/1) | 100% (1/1) | CJD+GSS | Takada et al. 2017 | |
| 12-OPRI | N/A | 3 | Cog, Behav, Cbr Atx, Sz | 44 ± 1 (43–45) | 8 ± 1.7 (7–10) yr | 100% (3/3) | 0% (0/1) | 100% (1/1) | 0% (0/1) | 0% (0/1) | multicentric PrP-Plqs | GSS | Kumar et al. 2011 |
AD, Alzheimer-type dementia; Atx, ataxia; Behav, behavioral changes; Cbr, cerebellar; Cog, cognitive; D, dementia; Dep, depression; FHx, family history; Front, frontal lobe dysfunction; M, methionine; mo, months; Myo, myoclonus; N/A, not available; Neu, neuronal; OPRD, octapeptide repeat deletion; OPRI, octapeptide repeat insertion mutation; Path, pathology; PrP-Plqs, PrP-amyloid plaques; PSWC, periodic sharp wave complexes; Psy, psychiatric changes; RPD, rapidly progressive dementia; Sz, seizures; V, valine; Vac, vacuolation; Visuosp, visuospatial; yr, years.
aData on age at onset and duration of disease are shown as mean ± SD (range), unless otherwise indicated.
bPositive family history of dementia with similar clinical features (as of the proband) or PrD. For UCSF family history (FHx) Score scale: 0 when there was no positive FMH 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.
cIn most laboratories, Total tau is considered positive for prion disease if greater than 1150 or 1200 pg/mL.
dAccording to most commonly used European 2009 and UCSF 2011 criteria (Zerr et al. 2009; Vitali et al. 2011).
eIf there are differences between data published in the literature from the more recently published UCSF cohort, this information is provided in the table separately for that mutation.
fSome patients still alive, so duration at last follow-up.