Longitudinal clinical follow-up of a large family with the R357P Twinkle mutation

JAMA Neurol. 2013 Nov;70(11):1425-8. doi: 10.1001/jamaneurol.2013.3185.

Abstract

Importance: Autosomal dominant progressive external ophthalmoplegia due to PEO1 mutations is considered relatively benign, but no data about long-term progression of this disease have been reported. The aim of this study was to provide a 16-year clinical follow-up of autosomal dominant progressive external ophthalmoplegia due to the p.R357P gene mutation in PEO1.

Observations: Twenty-two members of an Irish-American family were examined in 1996, when PEO1 sequencing revealed a c.1071G>C/p.R357P mutation in 9 of them. We reexamined the family in 2012 using a standardized clinical protocol. Autosomal dominant progressive external ophthalmoplegia due to the p.R357P PEO1 mutation is a late-onset ocular myopathy beginning with ptosis and progressing slowly. Ophthalmoparesis, if present, is mild and evident only by neurological examination.

Conclusions and relevance: Our results are important for prognosis and genetic counseling.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / genetics*
  • Blepharoptosis / genetics*
  • DNA Helicases / genetics*
  • Family Health
  • Female
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Mutation / genetics*
  • Ocular Motility Disorders / genetics*
  • Proline / genetics*

Substances

  • Mitochondrial Proteins
  • Arginine
  • Proline
  • DNA Helicases
  • TWNK protein, human