Leber hereditary optic neuropathy
Gene: DNAJC30DNAJC30 has been demoted to Grey on this panel, because in the October 2022 test directory, the single gene test for DNAJC30 was removed from the Leber hereditary optic neuropathy (R42) clinical indication and was moved to the Optic neuropathy (R41) panel (this change was visible in the April 2023 data release of PanelApp).Created: 4 Mar 2024, 3:34 p.m. | Last Modified: 4 Mar 2024, 3:34 p.m.
Panel Version: 2.9
The gene-checked tag has been removed, as this gene is now associated with Leber-like hereditary optic neuropathy, autosomal recessive 1, (OMIM:619382).Created: 20 Feb 2024, 5:55 p.m. | Last Modified: 20 Feb 2024, 5:55 p.m.
Panel Version: 2.8
Comment on publications: Added publication (PMID: 35091433) describing a further 35 individuals from 32 families with Leber hereditary optic neuropathy (or other autosomal inherited optic atrophies) and homozygous or compound heterozygous, putatively pathogenic DNAJC30 variants.Created: 7 Nov 2022, 4:58 p.m. | Last Modified: 7 Nov 2022, 4:58 p.m.
Panel Version: 1.12
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 8 Mar 2022, 10:38 a.m. | Last Modified: 8 Mar 2022, 10:38 a.m.
Panel Version: 1.11
Comment on list classification: Promoted from Red to Amber. This gene is not associated with any phenotypes in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease assocation. This gene should be rated Green at the next review.Created: 18 Mar 2021, 4:43 p.m. | Last Modified: 18 Mar 2021, 4:43 p.m.
Panel Version: 1.8
33 individuals from 29 families had homozygous DNAJC30 missense variants. Three different variants identified (one responsible for most cases0.
All three variants not seen in gnomAD.
Incomplete penetrance and male predominance in affected individuals both typical of LHON due to mtDNA mutations
All 3 variants in the J domain of the protein.
Good functional evidence also providedCreated: 12 Feb 2021, 4:31 a.m. | Last Modified: 12 Feb 2021, 4:31 a.m.
Panel Version: 1.7
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Leber Hereditary Optic Neuropathy
Publications
Following to ESHG 2020 conference presentation, same study group published their findings in JCI journal. They identified additional families with affected individuals presenting as LHON-like phenotype. In total 33 affected individuals reported, with 29 harboured p.Tyr51Cys homozygous variant; remaining 4 patients, harboured p.Pro78Ser, p.Leu101Gln homozygous variants.
Study group showed Complex I deficiency in skeletal muscle biopsy studies; they performed functional assays to prove DNAJC30 pathogenicity.
Source: Publication (PMID: 33465056)Created: 4 Feb 2021, 10:20 a.m. | Last Modified: 4 Feb 2021, 10:20 a.m.
Panel Version: 1.7
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
LHON-like
Publications
Mode of pathogenicity
Other
Comment on list classification: Demoting from Green to Grey as this gene has been removed from the R42 (Leber hereditary optic neuropathy) clinical indication in v4 of the National Genomic Test Directory (October 2022).Created: 23 Nov 2022, 1:02 p.m. | Last Modified: 23 Nov 2022, 1:02 p.m.
Panel Version: 1.13
ESHG 2020 conference presentation - C25.5 - Impaired complex I repair causes recessive Leber’s hereditary optic neuropathy - Sarah Stenton et al. Report 29 families with individuals with biallelic variants in DNAJC30 and a Leber's hereditary optic neuropathy. 27 of the families have the same p.Tyr51Cys variant and come from Eastern Europe. Analysis suggests a founder mutation from 85 generations agao. 2 other variants found in other families p.Pro78Ser and p.Leu101Gln. Pentrance is not complete.
No publication relating to this work is found in PubMed at this time.
Sources: LiteratureCreated: 21 Jun 2020, 5:52 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Leber hereditary optic neuropathy
Tag curated_removed tag was added to gene: DNAJC30.
Publications for gene: DNAJC30 were set to 33465056; 35091433
Tag gene-checked was removed from gene: DNAJC30.
Gene: dnajc30 has been removed from the panel.
Publications for gene: DNAJC30 were set to 33465056
Tag gene-checked tag was added to gene: DNAJC30.
Tag Q2_21_rating was removed from gene: DNAJC30. Tag Q2_21_NHS_review was removed from gene: DNAJC30.
Source Expert Review Green was added to DNAJC30. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: DNAJC30 were changed from Leber hereditary optic neuropathy; LHON-like to Leber hereditary optic neuropathy, MONDO:0010788; LHON-like
Gene: dnajc30 has been classified as Amber List (Moderate Evidence).
Tag watchlist was removed from gene: DNAJC30. Tag Q2_21_rating tag was added to gene: DNAJC30. Tag Q2_21_NHS_review tag was added to gene: DNAJC30.
Phenotypes for gene: DNAJC30 were changed from Leber hereditary optic neuropathy to Leber hereditary optic neuropathy; LHON-like
Publications for gene: DNAJC30 were set to
gene: DNAJC30 was added gene: DNAJC30 was added to Leber hereditary optic neuropathy. Sources: Literature watchlist tags were added to gene: DNAJC30. Mode of inheritance for gene: DNAJC30 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAJC30 were set to Leber hereditary optic neuropathy Review for gene: DNAJC30 was set to RED