Description
Periodic fever syndromes and amyloidosis eligibility statement:

Periodic fever syndromes and amyloidosis inclusion criteria (29721)
- Biopsy proven amyloid deposition in any organ OR
- Recurrent or continuous attacks of systemic inflammation with evidence of a significantly raised CRP (> 30 mg/L with attacks) and at least 2 of the following features: onset before age 40, family history of similar symptoms, rash, fever > 38°C, serositis (synovial, peritoneal, pleuritic, pericardial or meningitic), arthralgia/myalgia, arthritis.

Periodic fever syndromes and amyloidosis exclusion criteria (29721)
- Evidence of underlying infectious, autoimmune or malignant cause
- Paraproteinaemia or haematological dyscrasia
- Known monogenic cause of periodic fever syndrome or amyloidosis

Prior genetic testing guidance (29721)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Periodic fever syndromes and amyloidosis prior genetic testing genes (29721)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 - FGA, apolipoprotein A-I, lysozyme,
 - If recurrent or continuous inflammation: MEFV, MVK, TNFRSFIA, NLRP3, NLRP12

Closing statement (29721)
These requirements will be kept under continual review during the main programme and may be subject to change.

5 reviewers

  • Tracy Briggs (Manchester Genomic Medicine Centre)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Sarah Leigh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Rebecca Foulger (Genomics England curator)

    Group: Other
    Workplace: Other

  • Alice Gardham (Genomics England)

    Group: Other
    Workplace: Other

  • Owen Siggs (Flinders University)

    Group: Other
    Workplace: Research lab

30 genes

30 reviewed, 20 green

List Gene Reviews Mode of inheritance Details
30 genes
Green Green List (high evidence)
APOA1
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
  • Eligibility statement prior genetic testing
Phenotypes
  • Amyloidosis 105200
Green Green List (high evidence)
APOA2
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Amyloidosis
Green Green List (high evidence)
ELANE
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
Phenotypes
  • Hereditary Periodic Fever Syndromes
  • Neutropenia, cyclic, 162800
  • Recurring fever and malaise
Tags
  • mosaicism
Green Green List (high evidence)
FGA
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
  • Eligibility statement prior genetic testing
Phenotypes
  • Amyloidosis, familial visceral 105200
Green Green List (high evidence)
GSN
1 review
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Amyloidosis
  • Amyloidosis, Finnish type, 105120
Green Green List (high evidence)
IL1RN
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Interleukin 1 receptor antagonist deficiency, 612852
  • OMPP
  • DIRA syndrome
  • recurrent fever
Green Green List (high evidence)
IL36RN
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Psoriasis 14, pustular, 614204
  • DITRA
  • recurrent flares of pustular rash with fever
Green Green List (high evidence)
LPIN2
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
Phenotypes
  • Hereditary Periodic Fever Syndromes
  • Majeed syndrome, 609628
Green Green List (high evidence)
LYZ
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyloidosis, renal, 105200
  • Familial Visceral Amyloidosis
Green Green List (high evidence)
MEFV
3 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
Phenotypes
  • Hereditary Periodic Fever Syndromes
  • Familial Mediterranean Fever
  • Familial Mediterranean fever, AD, 134610
  • Familial Mediterranean fever, AR, 249100
Green Green List (high evidence)
MVK
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
Phenotypes
  • Hereditary Periodic Fever Syndromes
  • Mevalonate kinase deficiency
  • Hyper-IgD syndrome, 260920
  • Mevalonic aciduria, 610377
Green Green List (high evidence)
NLRP12
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
Phenotypes
  • Familial cold autoinflammatory syndrome 2
  • 611762
Green Green List (high evidence)
NLRP3
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
Phenotypes
  • Hereditary Periodic Fever Syndromes
  • CINCA syndrome (NOMID), 607115
  • Familial cold-induced inflammatory syndrome 1 (FCAS), 120100
  • Muckle-Wells syndrome (MWS), 191900
Green Green List (high evidence)
NOD2
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Blau syndrome, 186580
Green Green List (high evidence)
OSMR
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amyloidosis, primary localized cutaneous, 1, 105250
Green Green List (high evidence)
OTULIN
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) (617099)
  • Otulin-related autoinflammatry syndrome (ORAS)
Green Green List (high evidence)
PSMB8
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Autoinflammation, lipodystrophy, and dermatosis syndrome 256040 (Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome) and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE syndrome))
Green Green List (high evidence)
PSTPIP1
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
Phenotypes
  • Hereditary Periodic Fever Syndromes
  • PAPA syndrome
  • Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, 604416
Green Green List (high evidence)
TNFRSF1A
3 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert Review Green
Phenotypes
  • Hereditary Periodic Fever Syndromes
  • Periodic fever, familial, 142680
Green Green List (high evidence)
TTR
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • UKGTN
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Amyloidosis, Hereditary, Transthyretin-Related, 105210
  • Familial Transthyretin Amyloidosis
Amber Amber List (moderate evidence)
APOC2
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Amyloidosis
  • Hyperlipoproteinemia, type Ib 207750
Amber Amber List (moderate evidence)
APOC3
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Amyloidosis
Amber Amber List (moderate evidence)
TNFAIP3
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
Phenotypes
  • Autoinflammatory syndrome, familial, Behcet-like
  • (AISBL) (616744)
Red Red List (low evidence)
APP
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants 605714
Red Red List (low evidence)
B2M
1 review
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
  • Literature
Phenotypes
  • ?Amyloidosis, familial visceral 105200
Red Red List (low evidence)
CST3
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
  • Literature
Phenotypes
  • Cerebral amyloid angiopathy 105150
Tags
  • founder-effect
Red Red List (low evidence)
HTR1A
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Other
Phenotypes
  • Periodic fever, menstrual cycle dependent, 614674
Red Red List (low evidence)
IL31RA
1 review
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Radboud University Medical Center, Nijmegen
  • Expert Review Red
Phenotypes
  • Amyloidosis, primary localized cutaneous, 2, 613955
Red Red List (low evidence)
NLRC4
1 review
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Other
Phenotypes
  • ?Familial cold autoinflammatory syndrome 4 616115
  • Autoinflammation with infantile enterocolitis 616050
Red Red List (low evidence)
TRNT1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Other
Phenotypes
  • Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, 616084

0 STRs

0 reviewed, 0 green

List STR Reviews Mode of inheritance Details
0 STRss

Major version comments

Downloads

Download lists

Download Version