Hereditary neuropathy or pain disorder

Gene: DCTN1

Green List (high evidence)

G59 mutation clearly causes dhmn with vocal cord palsy. Multiple unrelated families

Created: 9 May 2019, 12:16 p.m.

Green List (high evidence)

In Bristol seen 2 previously reported pathogenic variants (segregating in several family members) and one likely pathogenic variant (all had motor neuropathy). Should be included to pick up patients perhaps with ALS/MND who are presenting with motor neuropathy signs. PMID:27025386 (2016) - Study includes the report of a 12 year old boy with pure distal hereditary motor neuropathy with upper and lower limb weakness. PMID: 28251916 - de novo variant in patient with pes cavus, ataxia and dystonia. PMID: 24627108 - patient with HMSN2 (apparently segregating but cannot see pedigree)

Created: 29 Apr 2019, 12:30 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Neuropathy, distal hereditary motor, type VIIB 607641; Perry syndrome 168605; {Amyotrophic lateral sclerosis, susceptibility to}, 105400

Publications

• 27025386
• 28251916
• 24627108

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) . New evidence/re-evaluation of evidence - promotion to Green / New evidence - upgrade to Green

Created: 6 Dec 2019, 2:23 p.m. | Last Modified: 6 Dec 2019, 2:23 p.m.

Panel Version: 0.36

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, 2:22 p.m. | Last Modified: 6 Dec 2019, 2:22 p.m.

Panel Version: 0.36

Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.

Created: 9 May 2019, 5 p.m.

Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.

Created: 29 Apr 2019, 12:53 p.m.

Green List (high evidence)

Always a very difficult one for us to interpret when we find variants

Created: 29 Apr 2019, 9:20 a.m.

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Variants in this GENE are reported as part of current diagnostic practice

Comment on list classification: Await further families before including in diagnostic panel

Created: 8 Jul 2016, 3:41 a.m.

This gene is in the Charcot Marie Tooth Disease section in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual, for testing of dHMN.

Created: 10 Jun 2016, 1:23 p.m.

Red List (low evidence)

Single family described

Created: 8 Dec 2015, 3:05 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown