Hereditary neuropathy or pain disorder

Gene: PTRH2

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:02 p.m. | Last Modified: 24 Feb 2025, 5:02 p.m.

Panel Version: 6.148

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on phenotypes: OMIM phenotype accessed on 24 October 2025.

Created: 24 Oct 2025, 5:16 p.m. | Last Modified: 24 Oct 2025, 5:16 p.m.

Panel Version: 7.24

Comment on list classification: As reviewed by Alexander Rossor, there are multiple unrelated individuals presenting with peripheral neuropathy. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 26 Oct 2024, 7:58 p.m. | Last Modified: 26 Oct 2024, 7:58 p.m.

Panel Version: 5.96

PMID:39176129 reported two sisters presenting with a severe, length-dependent sensorimotor axonal neuropathy, associated with deafness and intellectual deficiency. They were identified with a biallelic novel likely pathogenic variant within PTRH2 (p.Gln85Arg). This publication also summarised previously reported cases. Of 19 cases previously described in literature, 14 patients had neuropathy (axonal or demyelinating).

This gene has been associated with relevant phenotypes in both OMIM (MIM #616263) and Gene2Phenotype (with 'definitive' rating on the DD panel). MIM #616263 includes demyelinating sensorimotor peripheral neuropathy as one of the clinical manifestations.

Created: 26 Oct 2024, 7:51 p.m. | Last Modified: 26 Oct 2024, 7:51 p.m.

Panel Version: 5.93

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, OMIM:616263; neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1, MONDO:8000012

Publications

• 39176129

I don't know

Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope but limited evidence / Broad phenotype but limited evidence? Only 2 cases in OMIM

Created: 7 Dec 2019, 12:03 a.m. | Last Modified: 7 Dec 2019, 12:03 a.m.

Panel Version: 0.86

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, 10:25 p.m. | Last Modified: 6 Dec 2019, 10:25 p.m.

Panel Version: 0.84

Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.

Created: 11 Jun 2019, 1:40 p.m.

Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.

Created: 11 Jun 2019, 1:40 p.m.

Green List (high evidence)

Peripheral neuropathy now reportedin multiple unrelated individuals and can be a presenting feature. Shouldbe green and in R78 panel

Created: 20 Oct 2024, 10:41 a.m. | Last Modified: 20 Oct 2024, 10:41 a.m.

Panel Version: 5.19

Only two families

Created: 6 Jun 2019, 10:52 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, sensory neuronal hearing loss, hepatomegaly, pancreatic insufficiency, proximal placement of thumb, SNCV neuropathy.

Publications

• 25572476
• 25558065: 28328138: 31057140: 27129381: 39176129: 38874107