HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Data Supplement Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kimber, E. Articles by Tulinius, M. Search for Related Content PubMed PubMed Citation Articles by Kimber, E. Articles by Tulinius, M. Related Collections Muscle disease All Genetics

A mutation in the fast skeletal muscle troponin I gene causes myopathy and distal arthrogryposis

From the Department of Neuropediatrics (E.K.), Uppsala University Children's Hospital, Uppsala, and Department of Pathology (H.T., A.O.), Sahlgrenska University Hospital, and Queen Silvia Children's Hospital (A.-K.K., M.T.), Sahlgrenska Academy at the University of Göteborg, Göteborg, Sweden.

Address correspondence and reprint requests to Dr. E. Kimber, Department of Neuropediatrics, Uppsala University Children's Hospital, S-751 85 Uppsala, Sweden; e-mail: eva.kimber{at}akademiska.se

Objective: To describe a three-generation family with distal arthrogryposis associated with myopathy and caused by a mutation in the gene encoding for sarcomeric thin filament protein troponin I, TNNI2.

Methods: The authors performed clinical investigations and reviewed medical records. Muscle biopsy specimens were obtained for morphologic analysis. Genomic DNA was extracted from blood and analyzed for mutations in TNNI2.

Results: The five affected individuals had predominantly distal congenital joint contractures, mild facial involvement (mild micrognathia, narrow palpebral fissures), and no detectable muscle weakness. The four affected adults had slightly increased levels of creatine kinase in blood, and muscle biopsy specimens showed findings of myopathy with changes restricted to type 2 fibers. These included variability of muscle fiber size, internalized nuclei, and increased interstitial connective tissue. Analysis of TNNI2 encoding the troponin I isoform expressed in type 2 muscle fibers disclosed a heterozygous three-base in-frame deletion, 2,918–2,920del, skipping the highly conserved lysine at position 176. The mutation was present in all 5 affected individuals but was not identified in any of the 11 unaffected family members.

Conclusion: Distal arthrogryposis type 1 is genetically heterogeneous, and myopathy due to sarcomeric protein dysfunction may be one underlying cause of the disease.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the August 22 issue to find the title link for this article.

Supported by grants from the Linnea and Josef Carlsson Foundation, the Health and Medical Care Executive Board of the Region Västra Götaland, and Swedish Research Council project no. 7122.

Disclosure: The authors report no conflicts of interest.

Received March 13, 2006.

Accepted in final form April 24, 2006.

This article has been cited by other articles:

				H. Tajsharghi, E. Kimber, A.-K. Kroksmark, R. Jerre, M. Tulinius, and A. Oldfors Embryonic Myosin Heavy-Chain Mutations Cause Distal Arthrogryposis and Developmental Myosin Myopathy That Persists Postnatally Arch Neurol, August 1, 2008; 65(8): 1083 - 1090. [Abstract] [Full Text] [PDF]