Case Report/Case Series |

Longitudinal Clinical Follow-up of a Large Family With the R357P Twinkle Mutation

Carmen Paradas, MD1,2,3; Pilar Camaño, PhD2,3,4,5; David Otaegui, PhD3,5; Oguzhan Oz, MD3; Valentina Emmanuele, MD3; Salvatore DiMauro, MD3; Michio Hirano, MD3
[+] Author Affiliations
1Unidad de Enfermedades Neuromusculares, Servicio de Neurología, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Seville, Spain
2Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Madrid, Spain
3Department of Neurology, Columbia University Medical Center, New York, New York
4Ilundain Haritz Berri Fundazioa, Valle de Aranguren, Spain
5Department of Neurosciences, BioDonostia Health Research Institute, Donostia Hospital, San Sebastián, Spain
JAMA Neurol. 2013;70(11):1425-1428. doi:10.1001/jamaneurol.2013.3185.
Text Size: A A A
Published online

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.

Figures in this Article

Sign In to Access Full Content

Don't have Access?

Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more

Subscribe for full-text access to content from 1998 forward and a host of useful features

Activate your current subscription (AMA members and current subscribers)

Purchase Online Access to this article for 24 hours


Place holder to copy figure label and caption
Figure 1.

Individual symbols have been partitioned and shaded with different fills. We differentiate symptoms (the patient is aware of the clinical manifestation) from signs (the clinical manifestation is revealed by physical examination). Arrow indicates proband.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Ptosis and External Ocular Movements After 16 Years of Follow-up

The photographs in the basal column were taken in primary eye position. In the next columns, we asked the patients to look up, down, left, and right to evaluate any restriction in eye movements.

Graphic Jump Location




Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment


Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics