Hereditary neuropathy or pain disorder
Gene: NTRK1
I agree with Zornitza Stark that it is a complex phenotype. However, neuropathy has been associated with the phenotype in sufficient number of cases and been reviewed by several expert reviewers. Hence, the rating should remain as Green.
This gene has been associated with relevant phenotypes in both OMIM (MIM #256800) and Gene2Phenotype (with 'definitive' rating in DD and skin panels).Created: 19 May 2023, 5:24 a.m. | Last Modified: 22 May 2023, 9:36 a.m.
Panel Version: 3.31
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Insensitivity to pain, congenital, with anhidrosis, OMIM:256800
This is a complex phenotype with anhidrosis and other ectodermal features, ID, fever and eye abnormalities in addition to the neuropathy. It is on our 'Neuropathy_complex' rather than our 'Neuropathy_isolated' virtual panel.Created: 1 Apr 2020, 9:22 a.m. | Last Modified: 1 Apr 2020, 9:22 a.m.
Panel Version: 1.4
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Insensitivity to pain, congenital, with anhidrosis, MIM# 256800
In Bristol two probands confirmed compound heterozygous pathogenic variants. PMID: 28940190 - Bristol paper including known nonsense and novel 9 amino acid in-frame deletion (bi-parental inheritance)Created: 29 Apr 2019, 12:30 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hereditary Neuropathies; Insensitivity to pain, congenital, with anhidrosis
Publications
Variants in this GENE are reported as part of current diagnostic practice
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.
Variants in this GENE are reported as part of current diagnostic practice
Comment on mode of inheritance: Source: G2P and OMIMCreated: 4 May 2016, 8:52 a.m.
Comment on list classification: Promoted from amber to green due to agreement from 3 reviewers.Created: 4 May 2016, 8:50 a.m.
HSNCreated: 9 Dec 2015, 8:49 a.m.
Variants in this GENE are reported as part of current diagnostic practice
HSNCreated: 8 Dec 2015, 3:05 p.m.
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: NTRK1 were changed from Hereditary Neuropathies; Insensitivity to pain, congenital, with anhidrosis to Hereditary Neuropathies; Insensitivity to pain, congenital, with anhidrosis, OMIM:256800
gene: NTRK1 was added gene: NTRK1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH,Expert list,Emory Genetics Laboratory,UKGTN,Expert Review Green,South West GLH Mode of inheritance for gene: NTRK1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NTRK1 were set to 28940190 Phenotypes for gene: NTRK1 were set to Hereditary Neuropathies; Insensitivity to pain, congenital, with anhidrosis