Hereditary neuropathy

Gene: DNAJC3

Green List (high evidence)

Comment on list classification: There is sufficient evidence (six unrelated families) available for promoting this gene to green rating in this panel.

Created: 28 Jul 2023, 3:12 p.m. | Last Modified: 28 Jul 2023, 3:13 p.m.

Panel Version: 1.472

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, 3:11 p.m. | Last Modified: 28 Jul 2023, 3:27 p.m.

Panel Version: 1.472

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

The Neurology Specialist Test Group agreed that this gene was recommended for the WGS panel based on a broader phenotype view to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. This panel includes conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation. This panel as going to be used for R78, 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 and as a result a new panel was created https://panelapp.genomicsengland.co.uk/panels/846/ for this purpose.

Created: 7 Dec 2019, 6:08 p.m. | Last Modified: 7 Dec 2019, 6:08 p.m.

Panel Version: 1.352

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