Hereditary neuropathy

Gene: TRPA1

I don't know

There are just 2 reports in the literature with variants in this gene. A missense variant has been associated with a neurologic disorder characterised by onset in infancy of episodic debilitating upper body pain triggered by fasting, cold and physical stress. Pathogenicity has been confirmed through segregation and functional analysis that shows a gain of function.

A truncating variant has been associated with carbamazepine responsive cramp-fasciculation syndrome in a father and son (PMID: 28436534). There is no other evidence to support pathogenicity of this variant and the variant has been seen heterozygously in 20 individuals in gnomad. The pLI for this gene is zero - suggesting LOF variants are tolerated.

As there is only one confirmed report in the literature this gene does not meet the criteria to be green and should be listed as amber.

Created: 15 Jun 2020, 12:11 p.m. | Last Modified: 15 Jun 2020, 12:11 p.m.

Panel Version: 1.368

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
episodic debilitating upper body pain triggered by fasting, cold and physical stress

Publications

• 20547126
• 25724085

Green List (high evidence)

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

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.

Green List (high evidence)