Hereditary ataxia with onset in adulthood
Gene: TWNK
On Sheffield panel. Overlaps with mitochondrial (PEO). 6 DM with Spinocerebellar ataxia, infantile onset in HGMD.Created: 27 Apr 2019, 7:39 p.m.
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.
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 mechanismCreated: 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
Source London North GMS was added to TWNK.
Added phenotypes Mitochondrial DNA depletion syndrome 7, 271245; Perrault syndrome 5, 616138; Progressive external ophthalmoplegia with mitochondrial DNA deletions, 609286 for gene: TWNK
Source NHS GMS was added to TWNK.
Source Wessex and West Midlands GLH was added to TWNK.
Louise Daugherty: Comment on phenotypes: Implica
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
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
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)