Tel: 1-631-626-9181 (USA)    44-207-097-1828 (Europe)


Official Full Name
chromosome 10 open reading frame 2
C10ORF2; chromosome 10 open reading frame 2; infantile onset spinocerebellar ataxia (autosomal recessive), IOSCA; twinkle protein, mitochondrial; FLJ21832; PEO; PEO1; twinkle; TWINL; ataxin 8; mitochondrial twinkle protein; T7-like mitochondrial DNA helicase; progressive external ophthalmoplegia 1 protein; T7 gp4-like protein with intramitochondrial nucleoid localization; SCA8; ATXN8; IOSCA; PEOA3; SANDO; MTDPS7; infantile onset spinocerebellar ataxia (autosomal recessive) , IOSCA

Recent Research Progress

Chromosome 10 open reading frame 2 (C10orf2), encodes the mitochondrial helicase Twinkle, also known as Twinkle or PEO1. The accumulation of multiple deletions in the mtDNA of affected tissues and an associated respiratory chain defect are caused by defects in C10orf2. Several studies have shown that a variety of autosomal recessive diseases are related to mutations in the C10orf2 gene. Currently, mutations in the C10orf2 gene have been documented in patients with clinical phenotypes, such as chronic progressive external ophthalmoplegia (CPEO), Parkinsonism, infantile-onset spinocerebellar ataxia (IOSCA), severe early onset encephalopathy, severe epileptic encephalopathy and mtochondrial DNA (mtDNA) depletion syndrome.

Mutations in the C10orf2 gene may lead to CPEO

CPEO is a genetic heterogeneous mitochondrial disease, usually occurring simultaneously with the characteristics of other variable diseases. It has been demonstrated that mutations in the nuclear genes involved in mtDNA replication and nucleotide metabolism may lead to CPEO, which is related to the loss of a variety of mtDNA in skeletal muscle. C10orf2 is essential for mtDNA replication, which encodes mitochondrial scintillating proteins. The Twinkle protein shows high amino acid sequence similarity with bacteriophage T7 gene 4 protein (T7 gp4), which comprises an N-terminal primase domain, a C-terminal helicase domain and an intervening linker region. More than 30 disease-causing mutations have been detected in Twinkle proteins, most of which affect the junction or helicase regions. Recent studies have shown that recessive mutations of homozygous and complex heterozygous in the helicase domain of C10orf2 gene can lead to the deletion of mtDNA. P.G655D, located in the helicase domain of C10orf2 gene, may play a role in multiple mtDNA deletions and CPEO.

Recessive mutations in C10orf2 are relevant in IOSCA

MI-Hyun Park et al. investigated the causative mutation in a Korean family with combined phenotypes of IOSCA, sensorimotor polyneuropathy, and myopathy. Compound heterozygous mutations c.1460C>T and c.1485-1G>A in C10orf2 were identified as causative of IOSCA. They found that the new complex hybrid mutation in the C10orf2 gene resulted in sensory motor polyneuropathy and myopathy IOSCA. Signs of motor neuropathy and myopathy were discovered for the first time in IOSCA patients with C10orf2 mutations. These results suggest that the clinical spectrum of IOSCA caused by C10orf2 mutations may be more variable than previously reported.

The mutation of C10orf2 may be related to PS

Perrault syndrome (PS) is a rare autosomal recessive condition characterized by deafness and gonadic dysgenesis. Recently, mutations in five genes, C10orf2, CLPP, HARS2, HSD17B4 and LARS2, have been identified as PS related. Two rare diallelic mutations in C10orf2 encode an important mitochondrial helicase Twinkle. According to the literature, mutations in C10orf2 could be correlated with PS type II with neurological symptoms (ataxia or neuropathy).

In recent years, C10orf2 has become a hot research topic, and studies have shown that the mutation of C10orf2 gene is related to many autosomal recessive diseases. Therefore, further study of C10orf2 gene is undoubtedly of great theoretical significance and potential application value to clinical diagnosis.


  1. Paramasivam A, et al. Novel mutation in C10orf2 associated with multiple mtDNA deletions, chronic progressive external ophthalmoplegia and premature aging. Mitochondrion, 2016, 26:81–85.
  2. Lerat J, et al. An Application of NGS for Molecular Investigations in Perrault Syndrome: Study of 14 Families and Review of the Literature. Hum Mutat, 2016, 37:1354–1362.
  3. Mi-Hyun Park, et al. Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy. Neurogenetics, 2014, 15:171–182.
  4. L.A.M. Demain, et al. Expanding the genotypic spectrum of Perrault syndrome. Clin Genet, 2017, 91: 302–312.
  5. Ołdak M, et al. Novel neuro-audiological fndings and further evidence for TWNK involvement in Perrault syndrome. J Transl Med, 2017, 15:25.
  6. Soldà G, et al. First Independent Replication of the Involvement of LARS2 in Perrault Syndrome by Whole-Exome Sequencing of an Italian Family. J Hum Genet. 2016, 61(4):295–300.
  7. Juliette B, et al. Abnormal Glycosylation Profile and High Alpha-Fetoprotein in a Patient with Twinkle Variants. JIMD reports, 2016, 29:109-113.
  8. Faruq M, et al. Novel mutations in typical and atypical genetic loci through exome sequencing in autosomal recessive cerebellar ataxia families. Clin Genet. 2014, 86:335–341.
  9. Dursun F, et al. A Novel Missense Mutation in the CLPP Gene Causing Perrault Syndrome Type 3 in a Turkish Family. J Clin Res Pediatr Endocrinol, 2016, 8(4):472-477.
  10. Asem M. Alkhateeb, et al. Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability. Metab Brain Dis, 2016, 31:901–907.

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!