Table 4.

Clinical and Pathological Phenotype of Patients Carrying a TBK1 LoF Mutation or Possibly Pathogenic Missense Mutation

Mutation	Origin	Gender	Clinical diagnosisa	Subtypeb	Family history	Age at onset (years)	Age at last examination/death (years)	Disease duration (months)	Additional information
Truncating mutations
p.Gln*2c	Spanish	Female	FTD	bvFTD		56	60	>53
p.Lys29Argfs*15	German	Male	FTD	PNFA + PSP		73	†77	48
p.Val97Phefs*2	Swedish	Male	ALS		+	62	†63		MND‐TDP
p.Arg117*	Italian	Male	FTD	bvFTD	+	67	†74	86
p.Arg127*	German	Female	ALS	Bulbar		70	Alive
p.Trp445*	Spanish	Female	FTD + CBS	PNFA/agramatic variant		78	84	>72
p.Gly272_Thr331delc	Belgian	Male	FTD	bvFTD	+	48	†50	29
p.Ser398Profs*11c	Belgian	Male	ALS	Bulbar	+	59	Alive	>75
p.Ala417*	Swedish	Female	FTD	bvFTD	+	68	†71	27	FTLD‐TDP type B
p.Thr462Lysfs*3	German	Male	ALS + D		+	74	†75	11	LMN>>UMN
p.Ser518Leufs*32c	Belgian	Female	ALS		+	64	†64	6
In‐frame deletions
p.Thr79del	Spanish	Male	FTD + ALS	bvFTD + bulbar		56	†58	18	FTLD‐MND‐TDP type B + argyrophylic grain disease (stage III)
p.Asp167delc	Belgian	Male	ALS			60	†61
p.Glu643delc	Belgian	Female	FTD + ALS	bvFTD + spinal	+	62	†74	136
p.Glu643delc	Belgian	Female	FTD	bvFTD	+	64	Alive	>109
p.Glu643delc	Belgian	Male	ALS	Bulbar	+	51	†53	20
p.Glu643delc	Belgian	Male	ALS			63	†66
p.Glu643delc	Belgian	Male	FTD	PPA	+	70	†73	42
p.Glu643delc	Belgian	Female	FTD	bvFTD		69	Alive	>99
Functional missense mutations
p.Leu94Ser	Bulgarian	Male	ALS	Spinal	+	44	55	>120	Slow disease progression
p.Gly121Aspc	Spanish	Male	ALS	Spinal		34	39	>60	Slow disease progression
p.Arg143Cys	German	Male	FTD	bvFTD		45
p.Arg229Ser	German	Male	ALS			47
p.Gly244Val	Portuguese	Female	FTD + ALS	Bulbar	+	41	†43		C9orf72 repeat expansion carrier
p.Ile246Thr	German	Female	ALS	Bulbar		57	†59
p.Lys291Gluc	Belgian	Male	FTD	bvFTD	+	52	†61
p.Ile418Val	Portuguese	Female	FTD	bvFTD	+	53	54

^aPresenting diagnosis or symptoms are listed first.

^bClinical subtype is given where documented. In FTD, the subtypes behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), progressive nonfluent aphasia (PNFA), semantic dementia (SD), and progressive supranuclear palsy (PSP) are specified where documented. In ALS, spinal or bulbar onset is specified where documented.

^cRefers to mutation carriers identified in the Belgian discovery cohort that were published earlier [Gijselinck et al., 2015; Van Mossevelde et al., 2015].

CBS, corticobasal syndrome; MND, motor neuron disease; LMN, lower motor neuron symptoms; UMN, upper motor neuron symptoms; D, unspecified dementia. +, a positive family history was documented.