Hereditary neuropathy or pain disorder

Gene: TTPA

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

TTPA variants have been associated with Ataxia with isolated vitamin E deficiency, OMIM:277460 and it is a definitive G2P gene for the same condition. Numerous TTPA variants have been reported in OMIM:277460 and it would appear that neuropathy is a common feature of this condition (PMID: 24369383).

Created: 5 Nov 2024, 5:59 p.m. | Last Modified: 5 Nov 2024, 5:59 p.m.

Panel Version: 6.108

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

I don't know

Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - ataxia with neuropathy / Broader phenotype: ataxia with vitamin E deficiency More likely to present as ataxia on ataxia panel

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 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.

Red List (low evidence)

Unable to find any evidence of clear neuropathy association

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

Phenotypes
Hereditary Neuropathies

I don't know

Green List (high evidence)

Eripheral neuropathy well established part of this complex phenotype. Now that R78 inlcudes complex phenotypes this gene should be included

Created: 20 Oct 2024, 10:56 a.m. | Last Modified: 20 Oct 2024, 10:56 a.m.

Panel Version: 5.19

Not a CMT gene

Created: 9 Dec 2015, 8:50 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Early onset ataxia and sensory axonal neuropathy similar to Friedreich ataxia, head titubation, normal fat absorption unlike abetalipoproteinaemia, rarely retinitis pigmentosa

Publications

• 24369383

Not a CMT gene

Created: 8 Dec 2015, 3:06 p.m.