Hereditary systemic amyloidosis
Gene: NLRP3Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.Created: 19 Oct 2020, 4:20 p.m. | Last Modified: 19 Oct 2020, 4:20 p.m.
Panel Version: 1.8
Comment on list classification: Updated rating from Grey to Green. NLRP3 was added to panel and rated Green by Zornitza Stark. Not yet in G2P but sufficient cases to support gene:disease association for NLRP3:Muckle-Wells syndrome, and approx 25-30% of MWS cases have an AA amyloidosis phenotype. Cases of NRLP3 variants in amyloidosis patients reported in PMIDs 30431487, 11992256. In summary: sufficient evidence to support association with MWS, and 25-30% of MWS patients have amyloidosis.Created: 25 Mar 2020, 10:09 p.m. | Last Modified: 25 Mar 2020, 10:09 p.m.
Panel Version: 1.7
PMID:11992256 (Dode et al., 2002) identify NLRP3 (CIAS1) variants in 9 unrelated families with MWS. AA amyloidosis is recorded amongst the phenotypes in family 1 (R260W variant).Created: 25 Mar 2020, 9:57 p.m. | Last Modified: 25 Mar 2020, 9:57 p.m.
Panel Version: 1.6
PMID:30431487 (Pandiarajan et al., 2018) report a 10-yr old child with nephrotic syndrome. The patient had a NLRP3 variant (c.1055C>T, p.Ala352Val) and features including AA amyloidosis.Created: 25 Mar 2020, 9:47 p.m. | Last Modified: 25 Mar 2020, 9:47 p.m.
Panel Version: 1.6
PMID:31057541 (Fingerhutová et al. 2019) report 1 family (11 individuals) with MWS and a p.Ala441Val variant in NLRP3. 2 patients aged over 50 years suffered with hearing loss and AA amyloidosis.Created: 25 Mar 2020, 9:47 p.m. | Last Modified: 25 Mar 2020, 9:47 p.m.
Panel Version: 1.6
PMID:27435956 (Villalba et al., 2016) report a 5-year old MWS patient with T348M variant in NLRP3. They report that amyloidosis and hearing loss is seen in ~25% of patients.Created: 25 Mar 2020, 9:47 p.m. | Last Modified: 25 Mar 2020, 9:47 p.m.
Panel Version: 1.6
PMID:28229991 (Hu et al., 2017) report a patient with periodic fever, arthralgia and skin lesions and an A92T variant in NLRP3 (p.D31V).Created: 25 Mar 2020, 9:47 p.m. | Last Modified: 25 Mar 2020, 9:47 p.m.
Panel Version: 1.6
PMID:11687797 (Hoffman et al., 2001) studied 1 family (family 4, 2 individuals) with MWS and a de novo C1055T (p.A352V) variant in NLRP3 (aka CIAS1). Arthrogryposis isn't specifically mentioned amongst phenotypes.Created: 25 Mar 2020, 9:47 p.m. | Last Modified: 25 Mar 2020, 9:47 p.m.
Panel Version: 1.6
Tag to_be_confirmed_NHSE tag was added to gene: NLRP3.
Phenotypes for gene: NLRP3 were changed from Muckle-Wells syndrome, 191900; AA amyloidosis; renal amyloidosis to Muckle-Wells syndrome, OMIM:191900; Renal amyloidosis
Gene: nlrp3 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: NLRP3.
Gene: nlrp3 has been classified as Green List (High Evidence).
Phenotypes for gene: NLRP3 were changed from Muckle-Wells syndrome, 191900 to Muckle-Wells syndrome, 191900; AA amyloidosis; renal amyloidosis
Publications for gene: NLRP3 were set to 11687797; 28229991; 27435956; 31057541
Phenotypes for gene: NLRP3 were changed from Muckle-Wells syndrome, 191900 to Muckle-Wells syndrome, 191900
Phenotypes for gene: NLRP3 were changed from Muckle-Wells syndrome to Muckle-Wells syndrome, 191900
gene: NLRP3 was added gene: NLRP3 was added to Amyloidosis. Sources: Expert list Mode of inheritance for gene: NLRP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NLRP3 were set to 11687797; 28229991; 27435956; 31057541 Phenotypes for gene: NLRP3 were set to Muckle-Wells syndrome Review for gene: NLRP3 was set to GREEN