Table 29.3.

PRNP nonsense mutations

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 FHx^a	CSF marker sensitivity		EEG PSWC	MRI c/w JCD^b	Neuropathology	Neuropathology pheno-type	References
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 FHx^a	14-3-3	Total tau	EEG PSWC	MRI c/w JCD^b	Neuropathology	Neuropathology pheno-type	References
Q145X	MM	1	Cog	38	21 years	0% (0/1)	N/A	N/A	N/A	N/A	NFT, PrP-angio	Atypic	Ghetti et al. (1996)
Q160X	MM (4) MV (3) Unknown (4)	11	D Cog, Dep Cog, dysauto, neuropathy	42.1±8.4 (32–59)	9.6±4.9 (4–21) years	100% (11/11)	0% (0/1)	0% (0/1)	0% (0/4)	0% (0/4)	NFT, PrP-angio, AD pathology	Atypical	Owen et al. (1989); Finckh et al.(2000) ; Jayadev et al. (2011); Fong et al., 2016
Q163X	Cis V (10)	10	Dysauto, neuropathy, Cog	33.0 ±3.4 (30–38)	26.8 ±8.0 (15–33) years	100% (10/10)	100% (1/1)	100%^d (1/1)	0% (0/3)	0% (0/2)	NFT, PrP-angio, PrP-Plaqs, Sp, V	Atypical	Mead et al. (2013)
Y226X	MV (2) Unknown (1)	3	D Park, Cog	55.3 ±17.0 (39–73)	3.5 ±2.3 (1.5–6) years	100% (3/3)	100% (1/1)	N/A	100% (1/1)	0% (0/1)	PrP-angio, PrP-Plaqs	Atypical	Jansen et al. (2010)
2bp Del 178	Unknown (3)	3	Dysauto, cog, neuropathy	42.0± 14.0 (26–52)	5.5± 6.4 (1–10) years	100% (3/3)	100% (2/2)	100% (1/1)	N/A	0% (0/2)	N/A	Atypical	Matsuzono et al. (2013)

From Kim et al. (2017) with permission from Cold Spring Harbor Laboratory Press.

Positive family history of dementia with similar clinical features (as of the proband) or prion disease.

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.

AD, Alzheimer-type dementia; Cog, cognitive; c/w, consistent with; D, dementia; Dep, depression; Dysauto, dysautonomia; EEG, electroencephalogram; FHx, family history; JCD, Jakob–Creutzfeldt disease; MRI, magnetic resonance imaging; N/A, not available; NFT, neurofibrillary tangles; Park, parkinsonism; PrP-angio, PrP amyloid angiopathy; PrP-Plqs, PrP-amyloid plaques; PSWC, periodic sharp-wave complexes; Sp, spongiosis; V, vacuolation.