Genes in panel

Hereditary ataxia - adult onset

Gene: TWNK

Green List (high evidence)

TWNK (twinkle mtDNA helicase)
EnsemblGeneIds (GRCh38): ENSG00000107815
EnsemblGeneIds (GRCh37): ENSG00000107815
OMIM: 606075, Gene2Phenotype
TWNK is in 18 panels

3 reviews

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

On Sheffield panel. Overlaps with mitochondrial (PEO). 6 DM with Spinocerebellar ataxia, infantile onset in HGMD.
Created: 27 Apr 2019, 7:39 p.m.

Louise Daugherty (Genomics England Curator)

I don't know

Review and rating submitted by James Polke (Neurogenetics Laboratory, Institute of Neurology, London) on behalf of London North GLH for GMS Neurology specialist test group
Created: 27 Apr 2019, 8:55 p.m.
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.

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

All OMIM phenotypes have been associated with cerebellar abnormalities and ataxia, although based on the experience of our mitochondrial team this is not a common feature of AD-PEO. Haploinsufficiency is not AD mechanism
Created: 15 Apr 2019, 10:06 a.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 7, 271245, Perrault syndrome 5, 616138, Progressive external ophthalmoplegia with mitochondrial DNA deletions, 609286

Mode of pathogenicity
Other - please provide details in the comments

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • London North GLH
  • NHS GMS
  • Wessex and West Midlands GLH
  • Expert Review Green
  • Hereditary ataxia v1.148
Phenotypes
  • Mitochondrial DNA depletion syndrome 7, 271245
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, 609286
  • Ataxia Neuropathy Spectrum Disorders, Dominant
  • Spinocerebellar Ataxia, Recessive
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, 609286
  • Perrault syndrome 5, 616138
  • Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245
OMIM
606075
Clinvar variants
Variants in TWNK
Penetrance
None
Panels with this gene

History Filter Activity

27 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GMS was added to TWNK.

15 Apr 2019, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Added phenotypes Mitochondrial DNA depletion syndrome 7, 271245; Perrault syndrome 5, 616138; Progressive external ophthalmoplegia with mitochondrial DNA deletions, 609286 for gene: TWNK

14 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to TWNK.

14 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Wessex and West Midlands GLH was added to TWNK.

9 Jan 2019, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Louise Daugherty: Comment on phenotypes: Implica

9 Jan 2019, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: TWNK were changed from Spinocerebellar Ataxia, Recessive; Ataxia Neuropathy Spectrum Disorders (Dominant); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, 609286; Perrault syndrome 5, 616138; Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245 to Spinocerebellar Ataxia, Recessive; Ataxia Neuropathy Spectrum Disorders, Dominant; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, 609286; Perrault syndrome 5, 616138; Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245

9 Jan 2019, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: TWNK were changed from Spinocerebellar Ataxia, Recessive; Ataxia Neuropathy Spectrum Disorders (Dominant) to Spinocerebellar Ataxia, Recessive; Ataxia Neuropathy Spectrum Disorders (Dominant); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, 609286; Perrault syndrome 5, 616138; Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245

15 Dec 2018, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Eleanor Williams (Genomics England Curator)

gene: TWNK was added gene: TWNK was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Green Mode of inheritance for gene: TWNK was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: TWNK were set to Spinocerebellar Ataxia, Recessive; Ataxia Neuropathy Spectrum Disorders (Dominant)