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Autoimmune Lymphoproliferative Syndrome v1.0 Zornitza Stark promoted panel to version 1.0
Autoimmune Lymphoproliferative Syndrome v0.32 RASGRP1 Zornitza Stark Marked gene: RASGRP1 as ready
Autoimmune Lymphoproliferative Syndrome v0.32 RASGRP1 Zornitza Stark Gene: rasgrp1 has been classified as Amber List (Moderate Evidence).
Autoimmune Lymphoproliferative Syndrome v0.32 STAT3 Zornitza Stark Marked gene: STAT3 as ready
Autoimmune Lymphoproliferative Syndrome v0.32 STAT3 Zornitza Stark Gene: stat3 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.32 Zornitza Stark Panel status changed from internal to public
Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Autoimmune Lymphoproliferative Syndrome v0.30 STAT3 Ain Roesley Classified gene: STAT3 as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.30 STAT3 Ain Roesley Gene: stat3 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.29 STAT3 Ain Roesley gene: STAT3 was added
gene: STAT3 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: STAT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STAT3 were set to 36228738
Phenotypes for gene: STAT3 were set to Autoimmune disease, multisystem, infantile-onset, 1 MIM#615952; STAT3-related early-onset multisystem autoimmune disease MONDO:0014414
Review for gene: STAT3 was set to GREEN
gene: STAT3 was marked as current diagnostic
Added comment: PMID:36228738;
Also known as STAT3 GoF syndrome, this review contains 191 patients with 72 unique variants
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.28 RASGRP1 Ain Roesley Classified gene: RASGRP1 as Amber List (moderate evidence)
Autoimmune Lymphoproliferative Syndrome v0.28 RASGRP1 Ain Roesley Gene: rasgrp1 has been classified as Amber List (Moderate Evidence).
Autoimmune Lymphoproliferative Syndrome v0.27 RASGRP1 Ain Roesley gene: RASGRP1 was added
gene: RASGRP1 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: RASGRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RASGRP1 were set to 29155103; 39752212
Phenotypes for gene: RASGRP1 were set to Immunodeficiency 64 MIM#618534
Review for gene: RASGRP1 was set to AMBER
gene: RASGRP1 was marked as current diagnostic
Added comment: PMID:29155103; 2 siblings Chet for Thr214Ile and Lys322*

PMID:39752212; 1x hom 'LoF' variant (unable to access paper)

PMID: 39278845; 1x patient from a cohort of autoimmune lymphoproliferative immunodeficiencies. Thr312Ala. did not indicate if homozygous or single hit

Amber due to quality of papers/journals
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.26 PRKCD Ain Roesley Marked gene: PRKCD as ready
Autoimmune Lymphoproliferative Syndrome v0.26 PRKCD Ain Roesley Gene: prkcd has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.26 PRKCD Ain Roesley Classified gene: PRKCD as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.26 PRKCD Ain Roesley Gene: prkcd has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.25 PRKCD Ain Roesley gene: PRKCD was added
gene: PRKCD was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: PRKCD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKCD were set to 37794137
Phenotypes for gene: PRKCD were set to Autoimmune lymphoproliferative syndrome, type III MIM#615559
Review for gene: PRKCD was set to GREEN
gene: PRKCD was marked as current diagnostic
Added comment: PMID:37794137; lit review with >10 families
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.24 LRBA Ain Roesley Marked gene: LRBA as ready
Autoimmune Lymphoproliferative Syndrome v0.24 LRBA Ain Roesley Gene: lrba has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.24 LRBA Ain Roesley Classified gene: LRBA as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.24 LRBA Ain Roesley Gene: lrba has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.23 LRBA Ain Roesley gene: LRBA was added
gene: LRBA was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: LRBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRBA were set to 38302222; 25931386
Phenotypes for gene: LRBA were set to Immunodeficiency, common variable, 8, with autoimmunity MIM#614700
Review for gene: LRBA was set to GREEN
gene: LRBA was marked as current diagnostic
Added comment: PMID:38302222; 5x in Center for Chronic Immunodeficiency in Freiburg, Germany database

PMID:25931386; 2 families in the report + 6 others in review table
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.22 CTLA4 Ain Roesley Marked gene: CTLA4 as ready
Autoimmune Lymphoproliferative Syndrome v0.22 CTLA4 Ain Roesley Gene: ctla4 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.22 CTLA4 Ain Roesley Classified gene: CTLA4 as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.22 CTLA4 Ain Roesley Gene: ctla4 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.21 CTLA4 Ain Roesley gene: CTLA4 was added
gene: CTLA4 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: CTLA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTLA4 were set to 39060684; 38302222
Phenotypes for gene: CTLA4 were set to Immune dysregulation with autoimmunity, immunodeficiency, and lymphoproliferation MIM#616100; autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency MONDO:0014493
Review for gene: CTLA4 was set to GREEN
gene: CTLA4 was marked as current diagnostic
Added comment: PMID: 39060684; 3x individuals. 1x missense, 1x splice 1x PTC

PMID:38302222; 9x in Center for Chronic Immunodeficiency in Freiburg, Germany database
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.20 ADA2 Ain Roesley Marked gene: ADA2 as ready
Autoimmune Lymphoproliferative Syndrome v0.20 ADA2 Ain Roesley Gene: ada2 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.20 ADA2 Ain Roesley Classified gene: ADA2 as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.20 ADA2 Ain Roesley Gene: ada2 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.19 ADA2 Ain Roesley gene: ADA2 was added
gene: ADA2 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: ADA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADA2 were set to 39060684; 29271561; 30692987; 34721429
Phenotypes for gene: ADA2 were set to Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome MIM#615688
Review for gene: ADA2 was set to GREEN
gene: ADA2 was marked as current diagnostic
Added comment: PMID:39060684; 1x individual hom for Gly358Arg. 4x path in clinvar

PMID:29271561; 1x individual hom for c.882-2A>G. 5-year-old female who presented with features that mimicked autoimmune lymphoproliferative syndrome (ALPS) in the absence of classic features of DADA2

PMID:34721429; 2 sibs Chet for Leu188Phe and Thr187Pro and both had complete absence of inosine, an adenosine-derived product.
Leu188Phe is absent in gnomad v4 and clinvar. high conservation + 0.9 REVEL
Thr187Pro 1 het 0 homs in v4 and 1x clinvar citing this paper high conservation + 0.7 REVEL

PMID:30692987 ; 1x Chet Tyr456Cys and Trp399*. The missense 1x LP in clinvar by Invitae and 2 hets 0 homs in v4. high conservation + REVEL 0.7
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.18 NRAS Ain Roesley Marked gene: NRAS as ready
Autoimmune Lymphoproliferative Syndrome v0.18 NRAS Ain Roesley Gene: nras has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.18 NRAS Ain Roesley Classified gene: NRAS as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.18 NRAS Ain Roesley Gene: nras has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.17 NRAS Ain Roesley gene: NRAS was added
gene: NRAS was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: NRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRAS were set to 39060684; 17517660; 33011939
Phenotypes for gene: NRAS were set to autoimmune lymphoproliferative syndrome type 4 MONDO:0013767
Review for gene: NRAS was set to GREEN
gene: NRAS was marked as current diagnostic
Added comment: PMID:39060684; 1x individual with Gly13Asp

PMID:17517660; 1x de novo GoF variant Gly13Asp.
NB: PMID:21079152 states that the paper above is a somatic variant. However, lymphoblasts, monocytes, and buccal epithelial cells, all demonstrating a heterozygous variant

PMID:33011939; review with 11x individuals
Gly13Asp, Gly12Val, Gly12Ser, Gly13Cys
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.16 MAGT1 Ain Roesley Marked gene: MAGT1 as ready
Autoimmune Lymphoproliferative Syndrome v0.16 MAGT1 Ain Roesley Gene: magt1 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.16 MAGT1 Ain Roesley Classified gene: MAGT1 as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.16 MAGT1 Ain Roesley Gene: magt1 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.15 MAGT1 Ain Roesley gene: MAGT1 was added
gene: MAGT1 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: MAGT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MAGT1 were set to 39060684; 25956530; 34447369
Phenotypes for gene: MAGT1 were set to Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia MIM#300853
Review for gene: MAGT1 was set to GREEN
gene: MAGT1 was marked as current diagnostic
Added comment: >5 unrelated males with ALPS-like
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.14 KRAS Ain Roesley Marked gene: KRAS as ready
Autoimmune Lymphoproliferative Syndrome v0.14 KRAS Ain Roesley Gene: kras has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.14 KRAS Ain Roesley Classified gene: KRAS as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.14 KRAS Ain Roesley Gene: kras has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.13 KRAS Ain Roesley gene: KRAS was added
gene: KRAS was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: KRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRAS were set to 27577878; 39060684; 21079152
Phenotypes for gene: KRAS were set to RAS-associated autoimmune leukoproliferative disorder MIM#614470
Review for gene: KRAS was set to GREEN
gene: KRAS was marked as current diagnostic
Added comment: Recurrent variant Gly13Cys

PMID:39060684
2x individuals with atypical ALPS - Gly13Cys

PMID:27577878
1x de novo mosaic in blood individual with ALPS - Gly13Cys

PMID:21079152
1x individual with ALPS-like syndrome somatic for Gly13Cys
1x individual with ALPS-like syndrome somatic for Gly12Asp
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.12 ITK Ain Roesley Marked gene: ITK as ready
Autoimmune Lymphoproliferative Syndrome v0.12 ITK Ain Roesley Gene: itk has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.12 ITK Ain Roesley Classified gene: ITK as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.12 ITK Ain Roesley Gene: itk has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.11 ITK Ain Roesley gene: ITK was added
gene: ITK was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: ITK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITK were set to 19425169; 22289921; 25061172; 26056787; 9311799; 10213685
Phenotypes for gene: ITK were set to Lymphoproliferative syndrome 1 MIM#613011
Review for gene: ITK was set to GREEN
gene: ITK was marked as current diagnostic
Added comment: 7 individuals from 5 unrelated families reported homozygous (missense/ nonsense) ITK variants consistent with Lymphoproliferative syndrome phenotype.

Two ITK-deficient mouse models demonstrated reduced T cells (CD4+), causing decreased CD4 to CD8 ratio.

Patients displayed early onset of features typically including fever, lymphadenopathy, autoimmune disorders, low immunoglobulins and high EBV viral load.
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.10 FASLG Ain Roesley Classified gene: FASLG as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.10 FASLG Ain Roesley Gene: faslg has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.9 FASLG Ain Roesley gene: FASLG was added
gene: FASLG was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: FASLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FASLG were set to 16627752; 17605793; 19794494; 8787672; 22857792; 33356695; 26334989; 25451160
Phenotypes for gene: FASLG were set to Autoimmune lymphoproliferative syndrome, type IB MIM#601859
Review for gene: FASLG was set to GREEN
gene: FASLG was marked as current diagnostic
Added comment: Sufficient evidence for AR gene-disease association. Limited evidence for AD gene-disease association
PMID: 22857792, 16627752, 26334989, 25451160 - 4 unrelated ALPS families reported with biallelic variants with a loss of function mechanism
PMID: 11457890, 19794494 - supporting deficient mouse models
PMID: 8787672, 17605793 - a single case (p.Met158_Glu185del) and a single family (p.Arg156Gly) reported with heterozygous variants, supporting dominant inheritance of dominant-negative variants. Another case reported with a rare VUS (p.Met86Val) that didn't alter protein function.
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.8 FADD Ain Roesley Marked gene: FADD as ready
Autoimmune Lymphoproliferative Syndrome v0.8 FADD Ain Roesley Gene: fadd has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.8 FADD Ain Roesley Classified gene: FADD as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.8 FADD Ain Roesley Gene: fadd has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.7 FADD Ain Roesley gene: FADD was added
gene: FADD was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: FADD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FADD were set to 21109225; 25794656; 32350755; 32971525
Phenotypes for gene: FADD were set to FADD-related immunodeficiency MONDO:0013408
Review for gene: FADD was set to GREEN
gene: FADD was marked as current diagnostic
Added comment: 3 families reported so far. 2 apparently unrelated consanguineous Pakistani families with autoimmune lymphoproliferative syndrome both segregating homozygous p.Cys105Trp. A single compound het case with p.Cys105Arg and a frameshift variant. Also, FADD deficient mouse models support a role in immunodeficiency. Null mice are embryonic lethal.
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.6 CASP10 Ain Roesley Marked gene: CASP10 as ready
Autoimmune Lymphoproliferative Syndrome v0.6 CASP10 Ain Roesley Gene: casp10 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.6 CASP10 Ain Roesley Classified gene: CASP10 as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.6 CASP10 Ain Roesley Gene: casp10 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.5 CASP10 Ain Roesley gene: CASP10 was added
gene: CASP10 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: CASP10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASP10 were set to 34329798; 34384744; 20301287
Phenotypes for gene: CASP10 were set to Autoimmune lymphoproliferative syndrome, type II MIM#603909
Review for gene: CASP10 was set to GREEN
gene: CASP10 was marked as current diagnostic
Added comment: Total of 15 individuals included in the review.

Asymptomatic carriers noted.
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.4 CASP8 Ain Roesley Marked gene: CASP8 as ready
Autoimmune Lymphoproliferative Syndrome v0.4 CASP8 Ain Roesley Gene: casp8 has been classified as Amber List (Moderate Evidence).
Autoimmune Lymphoproliferative Syndrome v0.4 CASP8 Ain Roesley Classified gene: CASP8 as Amber List (moderate evidence)
Autoimmune Lymphoproliferative Syndrome v0.4 CASP8 Ain Roesley Gene: casp8 has been classified as Amber List (Moderate Evidence).
Autoimmune Lymphoproliferative Syndrome v0.3 CASP8 Ain Roesley gene: CASP8 was added
gene: CASP8 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: CASP8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP8 were set to 12353035; 25814141; 12654726; 17213198; 16148088
Phenotypes for gene: CASP8 were set to Autoimmune lymphoproliferative syndrome, type IIB MIM#607271
Review for gene: CASP8 was set to AMBER
gene: CASP8 was marked as current diagnostic
Added comment: Amber due to functional studies

1 family (the 2nd family reported in PMID:25814141 was found to be distantly related to the one in PMID:12353035)

Mice with targeted T cell and B cell caspase-8 deficiency present normal thymocyte development but a marked decrease in peripheral blood T-cells. Besides, when challenged with the lymphocytic choriomeningitis virus (LCMV), these animals showed a significantly impaired immune response to the infection that included impaired CD8 cell expansion and an abrogated ability to generate virus-specific CD8+ cytotoxic T-cells.
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.2 FAS Ain Roesley Marked gene: FAS as ready
Autoimmune Lymphoproliferative Syndrome v0.2 FAS Ain Roesley Gene: fas has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.2 FAS Ain Roesley Classified gene: FAS as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.2 FAS Ain Roesley Gene: fas has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.1 FAS Ain Roesley gene: FAS was added
gene: FAS was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: FAS was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: FAS were set to Autoimmune lymphoproliferative syndrome, type IA MIM#601859
Review for gene: FAS was set to GREEN
gene: FAS was marked as current diagnostic
Added comment: Well established association
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.0 Ain Roesley Added Panel Autoimmune Lymphoproliferative Syndrome