Hereditary neuropathy or pain disorder
Gene: DNAJC3
Comment on list classification: There are six unrelated families with DNAJC3 biallelic variants and presenting with demyelinating sensorimotor peripheral neuropathy. Hence, this gene can be promoted to Green at the next GMS review.Created: 28 Jul 2023, 3:05 p.m. | Last Modified: 28 Jul 2023, 3:05 p.m.
Panel Version: 3.39
PMID:25466870 - Five individuals from two different families with demyelinating sensorimotor peripheral neuropathy and identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)).
PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with demyelinating sensorimotor peripheral neuropathy.
PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorimotor demyelinating and axonal polyneuropathy.
PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, of which patient 1 had demyelinating peripheral sensorimotor neuropathy.
PMID:34654017 - One of two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with demyelinating neuropathy.Created: 28 Jul 2023, 3:02 p.m. | Last Modified: 28 Jul 2023, 3:20 p.m.
Panel Version: 3.40
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, OMIM:616192
Publications
Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - minor feature / Broader phenotype - ataxia & hearing loss - only 1 family in OMIM - more evidence? Complex disorder not pure neuropathyCreated: 6 Dec 2019, 4:24 p.m. | Last Modified: 6 Dec 2019, 4:24 p.m.
Panel Version: 0.49
Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.Created: 6 Dec 2019, 4:23 p.m. | Last Modified: 6 Dec 2019, 4:23 p.m.
Panel Version: 0.49
Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.Created: 11 Jun 2019, 1:40 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Cerebellar ataxia, neuropathy with SNCV, hearing loss, diabetes mellitus
Publications
Publications for gene: DNAJC3 were set to 25466870; 28940199; 32738013; 3348646934654017
Gene: dnajc3 has been classified as Amber List (Moderate Evidence).
Tag Q3_23_promote_green tag was added to gene: DNAJC3.
Publications for gene: DNAJC3 were set to 25466870
Gene: dnajc3 has been classified as Amber List (Moderate Evidence).
gene: DNAJC3 was added gene: DNAJC3 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH Mode of inheritance for gene: DNAJC3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAJC3 were set to 25466870 Phenotypes for gene: DNAJC3 were set to Cerebellar ataxia, neuropathy with SNCV, hearing loss, diabetes mellitus; Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, 616192