Hereditary neuropathy or pain disorder

Gene: TRPV4

Green List (high evidence)

Multiple C5s in Bristol with specific phenotype including vocal cord involvement. Also well established from looking at HGMD. PubMed: 20037586 - Trpv4-knockout mice show sensorineural hearing loss and impairment of bladder voiding, suggesting that some clinical manifestations of HMSN2C may be due to loss of TRPV4 function as well as toxic gain of function. One reportedly HOMOZYGOUS loss-of-function variant in dHMN (https://www.biorxiv.org/content/10.1101/402388v2)

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

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

Phenotypes
other disorders; Hereditary motor and sensory neuropathy, type IIc, 606071

Publications

• 20037586

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

I don't know

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.

Comment on publications: corrected formating

Created: 30 Nov 2017, 10:51 a.m.

Green List (high evidence)

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

Green List (high evidence)

Publications

• PMID: 25900305 , PMID: 26392352

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, 1:50 p.m.

Is on the Charcot-Marie- Tooth disease type 2 / Intermediate CMT NGS Panel in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual.

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

Comment on mode of pathogenicity: Missense variants are relevant, and these will be reported in tier 2.

Created: 10 May 2016, 11:29 a.m.

Comment on list classification: Multiple reviewers agreeing this should be green, and diagnostically tested for.

Created: 10 May 2016, 11:24 a.m.

Green List (high evidence)

null mutations have been shown to be benign polymorphisms

Created: 9 Dec 2015, 8:48 a.m.

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

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments

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

Green List (high evidence)

null mutations have been shown to be benign polymorphisms

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

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

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments

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