Table 1.

A literature review focusing on pathogenic LRR variants was performed using the PubMed database. A total of 1113 articles were retrieved. After removing duplicates and excluding articles describing patients with mutations in the NACHT domain, those without genetic analysis, those describing previously reported patients, and those with other pathogenic mutations explaining the symptoms, a total of 18 articles describing 45 patients were included in the final analysis.

Article	Genotype	Sex	Age at Onset (Years Old)	Age at Diagnosis (Years Old)	Fever	Urticaria	Arthromyalgia and/or Arthritis	Meningitis	Uveitis and/or Papillary Edema	Hearing Loss *	Hearing Aids	Amyloidosis AA
[139]	p.G755R	M	Birth	N/D	+	+	+	N/D	+	N/D	N/D	+
[140]	p.G755R	N/D	Birth	N/D	+	+	+	+	+	1, Mild	N/D	N/D
[141]	p.G755R	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D
[142]	p.G755R	F	N/D	3	N/D	+	+	+	N/D	N/D	N/D	N/D
[143]	p.G755R	F	Birth	0.3	+	+	−	+	N/D	−	N/D	N/D
[144]	p.G755A	N/D	1	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D
[145]	p.G809S Ϯ	M	<1	N/D		+	+	+	N/D	−	−	N/D
[146]	p.K829T	M	2	20	+	−	−	N/D	−	+	N/D	N/D
[147]	p.Y859C	M	2	16	+	−	+	−	+	+, Moderate	+	N/D
[148]	p.Y859C	M	12	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D
[149]	p.Y859C	F	18	N/D	−	−	−	+	+	+, Severe	+	−
	p.Y859C	M	N/D	N/D	−	−	−	−	+	+, Moderate	N/D	−
[150]	p.Y859C	F	4	7	+	−	−	N/D	+	+, Moderate	N/D	N/D
[151]	p.Y859C	F	Childhood	38	+	+	+	N/D	N/D	+	N/D	N/D
[136]	p.Y859C	N/D	32	54	N/D	−	+	−	−	+	N/D	−
	p.Y859C	N/D	3	30	N/D	−	+	+	+	+	N/D	−
	p.Y859C	N/D	3	38	N/D	−		+	+	+	N/D	−
	p.Y859C	N/D	20	38	N/D	−	+	−	+	+	N/D	−
	p.Y859C	N/D	10	44	N/D	−	+	+	−	+	N/D	−
	p.Y859C	N/D	13	50	N/D	−	+	+	−	+	N/D	−
	p.Y859C	N/D	3	7	N/D	+	−	−	+	+	N/D	−
	p.Y859C	N/D	2	12	N/D	+	+	+	+	+	N/D	−
	p.Y859C	N/D		34	N/D	−	+	−	+	+	N/D	−
	p.Y859H	N/D		16	N/D	+	−	−	−	+	N/D	−
	p.Y859H	N/D	11	16	N/D	−	+	−	+	+	N/D	−
	p.Y859H	N/D	8	47	N/D	−	+	+	−	+	N/D	−
	p.Y859H	N/D	6	21	N/D	−	+	−	−	+	N/D	−
	p.Y859H	N/D		49	N/D	+	+	−	−	+	N/D	−
[125]	p.R918Q	F	9	N/D	+	−	+	N/D	N/D	+, Mild	−	N/D
[152,153]	p.R918Q	F	30	59	−	−	+	N/D	N/D	+, Moderate	N/D	N/D
	p.R918Q	F	N/D	69	−	−	−	N/D	N/D	+, Moderate	N/D	N/D
	p.R918Q	F	N/D	32	N/D	N/D	N/D	N/D	N/D	−	−	N/D
	p.R918Q	M	N/D	35	+	+	+	N/D	N/D	+, Moderate	N/D	N/D
	p.R918Q	M	N/D	13	+	N/D	N/D	N/D	N/D	+	N/D	N/D
	p.R918Q	F	N/D	10	+	+	N/D	N/D	N/D	+	N/D	N/D
	p.R918Q	M	N/D	6	+	+	N/D	N/D	N/D	−	−	N/D
	p.R918Q	F	N/D	70	N/D	N/D	N/D	N/D	+	+, Severe	N/D	N/D
	p.R918Q	M	N/D	60	N/D	N/D	N/D	N/D	+	+, Severe	N/D	N/D
	p.R918Q	D	N/D	50	N/D	N/D	N/D	N/D	+	+, Severe	N/D	N/D
	p.R918Q	D	N/D	40	N/D	N/D	N/D	N/D	+	+, Moderate	N/D	N/D
	p.R918Q	M	N/D	30	N/D	N/D	N/D	N/D	+	+, Moderate	N/D	N/D
	p.R918Q	M	N/D	40	N/D	N/D	N/D	N/D	+	+, Moderate	N/D	N/D
[154]	p.R918X	F	N/D	N/D	N/D	N/D	N/D	N/D	N/D	+, Severe	+	N/D
	p.R918X	F	1.5	N/D	N/D	N/D	N/D	N/D	N/D	+, Mild	N/D	N/D
[138]	p.L1016F #	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D

* Severity of hearing loss: mild if loss <40 dB, moderate if between 40 and 70 dB, severe if >70 dB or defined as so by the authors. Ϯ Heterozygous patient with a mutation in the NACHT domain (E688K). # In vitro analysis showed no gain-of-function of this mutation [135].