The TWNKgene encodes Twinkle, the primary DNA helicase responsible for mitochondrial DNA (mtDNA) replication. Twinkle is an ATP-dependent helicase that unwinds double-stranded mitochondrial DNA ahead of the replication machinery, allowing synthesis of new mitochondrial genomes. It is functionally analogous to the replicative helicases used during nuclear DNA replication, but it acts exclusively within mitochondria.
Mutations in TWNKgene can be autosomal dominant or recessive. Autosomal dominant mutation cause adult onset progressive external ophthalmoplegia while autosomal recessive disease in patients with both TWNK genes affected can cause infantile-onset spinocerebellar ataxia (IOSCA)
Some of the diseases associated with mutations in the TWNKgene include:
1. Autosomal dominant progressive external ophthalmoplegia (adPEO):It is a milder form of PEO that typically starts in adulthood. Symptoms include ptosis (droopy eyelids), difficulty moving the eyes, and weakness in other muscles.
2. Infantile-onset spinocerebellar ataxia (IOSCA)is a rare, progressive neurological and mitochondrial disease caoused by recessive mutations in the TWNKgene, as well as other genes involved in mitochondrial DNA maintanence. Infants with IOSCA develop normally for the first year of life before a cascade of degenerative symptoms begins. The signs and symptoms of IOSCA progress through childhood and adolescence, heavily affecting the central, peripheral, and autonomic nervous systems. Typical symptoms include ataxia, hypotonia, athetosis and relex loss, followed by opthalmoplegia and sensorineurol hearing loss.
TWNK