Hereditary neuropathy or pain disorder
Gene: TDP1
Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. Hence, it cannot be promoted to green rating.Created: 5 Apr 2023, 5:57 a.m. | Last Modified: 5 Apr 2023, 5:57 a.m.
Panel Version: 3.6
As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).
There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605).
This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.Created: 5 Apr 2023, 5:56 a.m. | Last Modified: 5 Apr 2023, 10:06 a.m.
Panel Version: 3.6
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250
Publications
TDP1(NM_018319.4):c.1478A>G p.(His493Arg) has now been reported in 3 separate families with significant segregation data (homozygous/consanguineous Arabic cases, 10 affected individuals, >>>20 meioses).
We have seen one WGS case with presumed compound heteorzygosity (parents not tested) for this variant + a predicted likely LOF variant.
Reported phenotype is combination of cerebellar ataxia and axonal neuropathy, with gait disturbance.Created: 27 Mar 2023, 12:37 p.m. | Last Modified: 27 Mar 2023, 12:37 p.m.
Panel Version: 3.2
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Variants in this GENE are reported as part of current diagnostic practice
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.
Bristol - no pathogenic or likely pathogenic variants out of approx.1900 patients tested. Not clearly associated with hereditary neuropathy. PMID: 12244316 - only report. Single family to date for the association with spinocerebellar ataxiaCreated: 29 Apr 2019, 12:30 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hereditary Neuropathies
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Single family reported to dateCreated: 8 Jul 2016, 4:23 a.m.
Comment on list classification: Seems to only have a single family to date for the association with spinocerebellar ataxia.Created: 4 May 2016, 9:27 a.m.
Spino cerebellar ataxia, single familyCreated: 9 Dec 2015, 8:49 a.m.
Spino cerebellar ataxiaCreated: 8 Dec 2015, 3:05 p.m.
Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Publications for gene: TDP1 were set to 12244316; 31182267
Tag founder-effect tag was added to gene: TDP1.
Phenotypes for gene: TDP1 were changed from Hereditary Neuropathies to ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250
Publications for gene: TDP1 were set to 12244316
gene: TDP1 was added gene: TDP1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,Expert list,Emory Genetics Laboratory,UKGTN,Expert Review Red,South West GLH Mode of inheritance for gene: TDP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TDP1 were set to 12244316 Phenotypes for gene: TDP1 were set to Hereditary Neuropathies