Gene: TWNK

Alternate names for this Gene: ATXN8|C10orf2|IOSCA|MTDPS7|PEO|PEO1|PEOA3|PRLTS5|SANDO|SCA8|TWINL

Gene Summary: This gene encodes a hexameric DNA helicase which unwinds short stretches of double-stranded DNA in the 5' to 3' direction and, along with mitochondrial single-stranded DNA binding protein and mtDNA polymerase gamma, is thought to play a key role in mtDNA replication. The protein localizes to the mitochondrial matrix and mitochondrial nucleoids. Mutations in this gene cause infantile onset spinocerebellar ataxia (IOSCA) and progressive external ophthalmoplegia (PEO) and are also associated with several mitochondrial depletion syndromes. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Gene is located in Chromosome: 10

Location in Chromosome : 10q24.31

Description of this Gene: twinkle mtDNA helicase

Type of Gene: protein-coding

rs386834145 in TWNK gene and Infantile onset spinocerebellar ataxia PMID 16135556 2005 Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky.

PMID 17722119 2007 Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion.

PMID 17921179 2007 Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion.

PMID 19853444 2009 Novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia and multisystem failure.

PMID 22353293 2012 A novel homozygous missense mutation c.1366C>G (L456V) in C10orf2 (the Twinkle gene) was identified, confirming infantile onset spinocerebellar ataxia in the probands.

PMID 22353293 2012 Identification of a novel Twinkle mutation in a family with infantile onset spinocerebellar ataxia by whole exome sequencing.

PMID 16135556 2005 This allele is expressed at a reduced level, causing the preponderance of messenger RNAs encoding Y508C polypeptides and thus leads to the IOSCA disease phenotype.

rs1554887213 in TWNK gene and Mitochondrial Diseases PMID 28812649 2017 Decreased male reproductive success in association with mitochondrial dysfunction.

rs369588002 in TWNK gene and PERRAULT SYNDROME 5 PMID 25355836 2014 Mutations in Twinkle primase-helicase cause Perrault syndrome with neurologic features.

rs111033572 in TWNK gene and Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions, Autosomal Dominant, 3 PMID 19353676 2009 Finding twinkle in the eyes of a 71-year-old lady: a case report and review of the genotypic and phenotypic spectrum of TWINKLE-related dominant disease.

PMID 17614277 2007 Mild ocular myopathy associated with a novel mutation in mitochondrial twinkle helicase.

PMID 11431692 2001 Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria.

PMID 16639411 2006 Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay.

PMID 15668446 2005 Sensory ataxic neuropathy due to a novel C10Orf2 mutation with probable germline mosaicism.

PMID 12163192 2002 Clinical and molecular features of adPEO due to mutations in the Twinkle gene.

PMID 12921794 2003 A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia.

PMID 18396044 2008 Phenotype and clinical course in a family with a new de novo Twinkle gene mutation.

PMID 18575922 2008 Novel Twinkle (PEO1) gene mutations in mendelian progressive external ophthalmoplegia.

PMID 19428252 2009 Molecular analysis in a family presenting with a mild form of late-onset autosomal dominant chronic progressive external ophthalmoplegia.

PMID 20479361 2010 The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO.

PMID 20880070 2011 TWINKLE gene mutation: report of a French family with an autosomal dominant progressive external ophthalmoplegia and literature review.