Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: LIG1

The 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

Green List (high evidence)

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

• 30395541

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

There does not seem to be consensus that this is a real disease gene so probably best kept out of this panel

Created: 29 Jun 2018, 2:22 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

I don't know

GRID V2.0
ESID Registry 20171117
Expert Review Amber

Created: 15 May 2018, 10:12 a.m.

I don't know

Added publication referenced by IUIS december 2019 update

Created: 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 1

Created: 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 associations

Created: 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: ENST00000263274

Created: 17 Apr 2018, 12:12 p.m.

Publications

• 30395541