Hereditary neuropathy or pain disorder

Gene: DNAJC3

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 9:32 a.m. | Last Modified: 2 May 2024, 9:32 a.m.

Panel Version: 4.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

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

• 25466870
• 28940199
• 32738013
• 33486469
• 34654017

I don't know

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 neuropathy

Created: 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.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebellar ataxia, neuropathy with SNCV, hearing loss, diabetes mellitus

Publications

• 25466870