Recessive MYF5 Mutations Cause External Ophthalmoplegia, Rib, and Vertebral Anomalies

Thymidine kinase 2 mutations in autosomal recessive progressive external ophthalmoplegia with multiple mitochondrial DNA deletions.

Autosomal-inherited progressive external ophthalmoplegia (PEO) is an adult-onset disease characterized by the accumulation of multiple mitochondrial DNA (mtDNA) deletions in post-mitotic tissues. Mutations in six different genes have been described to cause the autosomal dominant form of the disease, but only mutations in the DNA polymerase gamma gene are known to cause autosomal recessive PEO ...

Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance

Despite being a canonical presenting feature of mitochondrial disease, the genetic basis of progressive external ophthalmoplegia remains unknown in a large proportion of patients. Here we show that mutations in SPG7 are a novel cause of progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions. After excluding known causes, whole exome sequencing, targeted Sanger...

SLC25A4 and C10ORF2 Mutations in Autosomal Dominant Progressive External Ophthalmoplegia

BACKGROUND AND PURPOSE Progressive external ophthalmoplegia (PEO) with Mendelian inheritance is a heterogeneous group of diseases associated with multiple deletions of mitochondrial DNA (mtDNA), which results from the disturbed replication and maintenance of mtDNA secondary to the mutations of nuclear genes including POLG, SLC25A4, C10ORF2, POLG2, OPA1, and RRM2B. The aim of this study was to i...

Recessive twinkle mutations cause severe epileptic encephalopathy.

The C10orf2 gene encodes the mitochondrial DNA helicase Twinkle, which is one of the proteins important for mitochondrial DNA maintenance. Dominant mutations cause multiple mitochondrial DNA deletions and progressive external ophthalmoplegia, but recent findings associate recessive mutations with mitochondrial DNA depletion and encephalopathy or hepatoencephalopathy. The latter clinical phenoty...

Congenital external ophthalmoplegia.