Table 2.

Demographic and clinical characteristics of patients with TBK1 variants

Variant	Sex	Age of onset (years)	Family history	Disease duration (months)*	ALSFRS-R progression rate †	Site of onset	Phenotype16	Cognitive impairment25
p.Leu59Phefs*16‡	F	36	sALS	52 §	0.92	Spinal	Classic	No
c.358+5G>A‡	M	62	sALS	17	0.7	Spinal	PLMN	No
p.Asp118Asn¶	M	81	sALS	35 †	0.6	Spinal	PLMN	Yes (ALS-ECI)
p.Lys291Glu¶	M	74	sALS / Δ	33	0.57	Spinal	Flail arm**	Yes (ALS-NECI)
p.Arg357Gln¶	F	36	sALS	20	1.2	Spinal	Classic	No
p.Ile397Thr‡‡	M	65	sALS / ϕ	60	0.45	Spinal	Pyramidal	Yes (ALS-ECI)
c.1644–5_1644-2delAATA‡‡	M	43	sALS	26	2.9	Spinal	Pyramidal	No

*Disease duration: time from disease onset to latest visit or death.

†Progression rate = (48-ALSFRS-R score)/disease duration. 

‡Loss of function.

§Death.

¶Potentially pathogenic functional missense mutation.

**Hispanic ethnicity.

††Biological and pathogenetic relevance not clear by in vitro functional studies.

‡‡Not demonstrated as pathogenic.

ALSFRS-R, ALS Functional Rating Scale-revised; ALS-ECI, ALS with executive cognitive impairment; ALS-NECI, ALS with non-executive cognitive impairment; PLMN, pure lower motor neuron disease; sALS, sporadic amyotrophic lateral sclerosis; TBK1, TANK-binding kinase 1. 

Δ: a brother and a sister deceased approximately at the age of 75 years reported to be affected by unclassified dementia. Φ: mother deceased at the age of 90 years reported to be affected by unclassified dementia.