Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: LIG1The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 4 Mar 2022, 10:17 a.m. | Last Modified: 4 Mar 2022, 10:17 a.m.
Panel Version: 2.529
Comment on list classification: Changed rating from Green 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 (added 'for-review' tag).Created: 20 Oct 2020, 3:18 p.m. | Last Modified: 20 Oct 2020, 3:18 p.m.
Panel Version: 2.345
Comment on list classification: Updated rating from Red to Green. Red review pre-dates paper PMID:30395541 which provides 5 patients (3 kindreds) for evidence of association with immunodeficiency. Although severity of phenotype is variable, just sufficient cases for inclusion.Created: 30 Apr 2020, 9:30 a.m. | Last Modified: 30 Apr 2020, 9:30 a.m.
Panel Version: 2.139
PMID:30395541. Maffucci et al., 2018 report 5 patients form 3 kindreds with biallelic LIG1 variants and immunodeficiency of variable severity. Note that Sophie Hambelton's review pre-dates this IUIS paper, and LIG1 is on the IUIS 2019 update based on PMID:30395541.Created: 30 Apr 2020, 9:29 a.m. | Last Modified: 30 Apr 2020, 9:29 a.m.
Panel Version: 2.138
Five individuals from three families.Created: 11 Apr 2020, 3:36 a.m. | Last Modified: 11 Apr 2020, 3:36 a.m.
Panel Version: 2.51
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Combined immunodeficiency; Lymphopaenia; Hypogammaglobulinaemia; Recurrent bacterial and viral infections; Growth retardation; Sun sensitivity, radiation sensitivity; Macrocytosis
Publications
Variants in this GENE are reported as part of current diagnostic practice
There does not seem to be consensus that this is a real disease gene so probably best kept out of this panelCreated: 29 Jun 2018, 2:22 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
GRID V2.0
ESID Registry 20171117
Expert Review AmberCreated: 15 May 2018, 10:12 a.m.
Added publication referenced by IUIS december 2019 updateCreated: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.
Panel Version: 2.36
Comment on list classification: Changed from Amber to Red. Until further evidence from GRID this gene is rated Red. Also, External expert review notes Red status due to no consensus on gene pertinence for immunodeficiency.Created: 4 Jul 2018, 11:26 a.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): LIG1 .PanelApp HGNC gene symbol check: LIG1 . IUIS Disease: Ligase I deficiency . IUIS Inheritance: AR .T cells: T cell lymphopenia, reduced nave T cells, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Recurrent respiratory infections, growth retardation, sun sensitivity, lymphoma, radiation sensitivity. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: DNA Repair Defects other than those listed in Table 1Created: 2 Jul 2018, 10:35 a.m.
Kept as amber until further evidence in the literature or from external expert review input. Ligase I deficiency is associated to Recurrent respiratory infections but there is currently no confirmed gene-disease associationsCreated: 19 Jun 2018, 4:34 p.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.Created: 20 Apr 2018, 12:25 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: LIG1, PanelApp HGNC gene symbol check: LIG1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Other well defined PIDs / DNA-breakage disorder / DNA-ligase 1 ATP-dependent deficiency (LIG1)Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: LIG1, GRID_Gene_Symbol: LIG1, GRID_Transcript_ENS_Community submitted: ENST00000263274, GRID_Transcript_RefSeq: NM_000234.1, GRID_Transcript_ENS_used_on_Production: ENST00000263274Created: 17 Apr 2018, 12:12 p.m.
Publications
Tag for-review was removed from gene: LIG1.
Source Expert Review Green was added to LIG1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: lig1 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: LIG1.
Gene: lig1 has been classified as Green List (High Evidence).
Publications for gene LIG1 were updated from 32048120; 1581963; 32086639 to 30395541; 1581963; 32086639; 32048120
Source IUIS Classification December 2019 was added to LIG1. Added phenotypes Recurrent respiratory infections, growth retardation, sun sensitivity, lymphoma, radiation sensitivity; Combined immunodeficiencies with associated or syndromic features for gene: LIG1 Publications for gene LIG1 were updated from 1581963 to 32048120; 1581963; 32086639
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Gene: lig1 has been classified as Red List (Low Evidence).
Gene: lig1 has been classified as Red List (Low Evidence).
Phenotypes for gene LIG1 were set to DNA ligase I deficiency, DNA-ligase 1 ATP-dependent deficiency (LIG1), Recurrent respiratory infections, growth retardation, sun sensitivity, lymphoma, radiation sensitivity, Combined immunodeficiencies with associated or syndromic features
IUIS Classification February 2018 was added to LIG1. Panel: Primary immunodeficiency disorders
This gene has been classified as Amber List (Moderate Evidence).
Emory Genetics Laboratory was added to LIG1. Panel: Primary immunodeficiency disorders Literature was added to LIG1. Panel: Primary immunodeficiency disorders Phenotypes for gene LIG1 were set to DNA ligase I deficiency, DNA-ligase 1 ATP-dependent deficiency (LIG1) Publications for gene LIG1 was set to ['1581963']
Expert Review was added to LIG1. Panel: Primary immunodeficiency disorders Other was added to LIG1. Panel: Primary immunodeficiency disorders Phenotypes for gene LIG1 were set to DNA ligase I deficiency, DNA-ligase 1 ATP-dependent deficiency (LIG1)
LIG1 All sources for gene: LIG1 were removed
Expert Review Amber was added to LIG1. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to LIG1. Panel: Primary immunodeficiency disorders Phenotypes for gene LIG1 were set to DNA ligase I deficiency, DNA-ligase 1 ATP-dependent deficiency (LIG1)
Phenotypes for gene LIG1 were set to DNA ligase I deficiency
LIG1 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
LIG1 was created by Louise Daugherty