Hereditary neuropathy or pain disorder

Gene: DST

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? New evidence promote to Green

Created: 6 Dec 2019, 2:31 p.m. | Last Modified: 6 Dec 2019, 2:31 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, 1:19 p.m. | Last Modified: 6 Dec 2019, 1:19 p.m.

Panel Version: 0.12

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)

PMID:30371979 (Lys4330) in trans with the p.(Ala203Glu) in patient with adult form of HSAN type VI. Functional studies showed defects in actin cytoskeleton organization and consequent delayed cell adhesion, spreading and migration, while recombinant p.Ala203Glu dystonin loses the ability to bind actin. PMID:28468842 compound het variants in 3 affected sibs with HSAN-VI

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neuropathy, hereditary sensory and autonomic, type VI, 614653; others; Hereditary Sensory and Autonomic Neuropathy, Type VI; ?Neuropathy, hereditary sensory and autonomic, type VI

Publications

• 30371979
• 28468842

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

Red List (low evidence)

Comment on list classification: Amber gene demoted to red due to 3 reviewers in agreement.

Created: 4 May 2016, 8:44 a.m.

Green List (high evidence)

3 families, mouse model

Created: 16 May 2019, 3:07 p.m.

Homozygous truncating mutations cause epiidermolysis bullosa, homozygous truncating mutations reported in over severe infantile onset neurodegenerative condition

Created: 9 Dec 2015, 8:49 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Red List (low evidence)

Homozygous truncating mutations cause epiidermolysis bullosa, homozygous truncating mutations reported in over severe infantile onset neurodegenerative condition

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal