Membranoproliferative glomerulonephritis including C3 glomerulopathy
Gene: DGKE
A single paper (PMID: 23274426, Ozaltin et al 2013) reported proteinuric renal disease and a biopsy showing morphological features of MPGN (although no C3 and scanty immunoglobulin deposition) in 9 patients with biallelelic (mostly truncating) DGKE mutations. Heterozygous parents were unaffected.Created: 10 Jan 2020, 11:37 a.m. | Last Modified: 10 Jan 2020, 11:37 a.m.
Panel Version: 2.2
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Proteinuria; membranoproliferative glomerulonephritis
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on mode of inheritance: Changing the MOI to BIALLELIC, autosomal or pseudoautosomal as per the signed off version 2.13 (Oct 2020) and as agreed with NHSE.Created: 22 Nov 2022, 1:50 p.m. | Last Modified: 22 Nov 2022, 1:50 p.m.
Panel Version: 2.27
Comment on mode of inheritance: Reverting the mode of inheritance to BOTH monalllelic and biallelic to reflect the signed off version in March 2020. However, the recommendation is to change this to just BIALLELIC, following GMS review.Created: 19 Jan 2021, 2:54 p.m. | Last Modified: 19 Jan 2021, 2:54 p.m.
Panel Version: 2.16
Comment on mode of inheritance: Changing MOI to Biallelic only. All reported cases are homozygous.Created: 23 Mar 2020, 11:41 a.m. | Last Modified: 23 Mar 2020, 11:41 a.m.
Panel Version: 2.9
Recent review by Daniel Gale rates the gene green so no change in rating.
Checking mode of inheritance:
PMID: 23274426 - Ozaltin et al 2013 - 3 consanguineous families - 3 different homozygous variants in 9 individuals.
PMID: 28526779 - Azukaitis et al 2017 - review of 24 patients with aHUS/MPGN and variants in DGKE. The 9 cases with MPGN-like renal biopsies are those reported in Ozaltin et al 2013
Other papers cited by BRIDGE review are related to aHUS only (PMID: 23542698 and 21902819)
OMIM lists the mode of inheritance for Nephrotic syndrome, type 7, #615008 as AR.
Therefore, the mode of inheritance should be updated to BIALLELIC only.Created: 29 Jan 2020, 5:04 p.m. | Last Modified: 29 Jan 2020, 5:04 p.m.
Panel Version: 2.2
This gene was part of an initial gene list collated by Valerie Wilson, The National Renal Complement Therapeutics Centre, February 2019 on behalf of Yorkshire and North East GLH for the GMS Renal Specialist Test Group; Gene Symbol submitted: DGKE; Suggested initial gene rating: none provided;Created: 12 Feb 2019, 12:13 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Comment when marking as ready: Upgraded to green following the expert's advise (Dr Daniel Gale) give the recent publication (28526779)Created: 17 Dec 2017, 10:37 p.m.
Comment when marking as ready: Marked as amber as the recently published 28526779 described DGKE mutations in MPGN. To be upgraded as green following the expert reviewCreated: 15 Dec 2017, 4:18 p.m.
Novel gene currently associated to atypical haemolytic uraemic syndrome (aHUS), but are thought to be also causative for MPGN. PMID: 23542698 study of patients with atypical haemolytic uraemic syndrome, not PMG. Because of the variable expressivity of some complement gene mutations, we have included the genes known to cause (and in routine clinical testing in) the mechanistically related, extremely rare disease atypical Haemolytic Uraemic Syndrome (aHUS). There is now good evidence that mutations that are associated with aHUS can be found in patients with Primary MPGN/C3G (see Servais et al PMID: 22456601). Therefore known or clearly pathogenic mutations previously associated with aHUS would be presumed to be causative in patients with PMG where this is the clinical presentation.Created: 5 Jun 2017, 3:49 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Haemolytic uraemic syndrome; aHUS; Hemolytic uremic syndrome, atypical, susceptibility to, 7, 615008; Nephrotic syndrome, type 7, 615008; C3 glomerulopathy; C3G; Immune complex MPGN; IC-MPGN
Publications
Mode of inheritance for gene: DGKE was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Tag to_be_confirmed_NHSE tag was added to gene: DGKE.
Mode of inheritance for gene: DGKE was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tag for-review tag was added to gene: DGKE.
Mode of inheritance for gene: DGKE was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Source NHS GMS was added to DGKE. Rating Changed from Green List (high evidence) to Green List (high evidence)
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
15th December 2017. Panel reviews were assessed, and panel was revised according to reviews and further curation by Arianna Tucci and Louise Daugherty
This gene has been classified as Amber List (Moderate Evidence).
Publications for DGKE were set to 23274426; 23542698; 21902819; 28526779
Publications for DGKE were set to 23274426; 23542698; 21902819
This gene has been classified as Amber List (Moderate Evidence).
DGKE was added to Primary Membranoproliferative Glomerulonephritispanel. Sources: Expert list
DGKE was created by Anonymous