Hereditary ataxia with onset in adulthood
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. However, the additional patient reported by Ian Berry (Leeds Genetics Laboratory) had the same variant in compound heterozygous state with another novel variant. As there is an additional variant reported, this gene can be considered for promotion to GREEN rating at the next major review.Created: 5 Apr 2023, 5:48 a.m. | Last Modified: 24 Jul 2023, 1:23 p.m.
Panel Version: 4.15
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, 5:43 a.m. | Last Modified: 5 Apr 2023, 10:05 a.m.
Panel Version: 4.6
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, 12:36 p.m. | Last Modified: 27 Mar 2023, 12:36 p.m.
Panel Version: 4.1
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
PMID: 12244316; PMID: 31182267
Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.Created: 15 Apr 2019, 10:21 a.m.
Single homozygous missense variant reported in one family. Insufficient evidenceCreated: 15 Apr 2019, 10:06 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Autosomal recessive spinocerebellar ataxia with axonal neuropathy, 607250
Variants in this GENE are reported as part of current diagnostic practice
Tag Q3_23_promote_green tag was added to gene: TDP1.
Publications for gene: TDP1 were set to 12244316; 31182267
Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Tag founder-effect tag was added to gene: TDP1.
Phenotypes for gene: TDP1 were changed from Autosomal recessive spinocerebellar ataxia with axonal neuropathy, 607250; Spinocerebellar ataxia, autosomal recessive with axonal neuropathy to ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250
Publications for gene: TDP1 were set to 12244316; 31182267
Publications for gene: TDP1 were set to
Added phenotypes Autosomal recessive spinocerebellar ataxia with axonal neuropathy, 607250 for gene: TDP1
Source NHS GMS was added to TDP1.
Source Wessex and West Midlands GLH was added to TDP1.
Louise Daugherty: Comment on phenotypes: Implica
gene: TDP1 was added gene: TDP1 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red Mode of inheritance for gene: TDP1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TDP1 were set to Spinocerebellar ataxia, autosomal recessive with axonal neuropathy