SEPN1: Associated with congenital fiber-type disproportion and insulin resistance
Version of Record online: 19 DEC 2005
Copyright © 2005 American Neurological Association
Annals of Neurology
Volume 59, Issue 3, pages 546–552, March 2006
How to Cite
Clarke, N. F., Kidson, W., Quijano-Roy, S., Estournet, B., Ferreiro, A., Guicheney, P., Manson, J. I., Kornberg, A. J., Shield, L. K. and North, K. N. (2006), SEPN1: Associated with congenital fiber-type disproportion and insulin resistance. Ann Neurol., 59: 546–552. doi: 10.1002/ana.20761
- Issue online: 17 FEB 2006
- Version of Record online: 19 DEC 2005
- Manuscript Revised: 25 OCT 2005
- Manuscript Accepted: 25 OCT 2005
- Manuscript Received: 19 JUL 2005
- National Health and Medical Research Council of Australia. Grant Numbers: 139039, 206529
- Muscular Dystrophy Association of New South Wales, Australia
Our first objective was to determine whether SEPN1 gene mutations are a cause of congenital fiber-type disproportion (CFTD), a rare form of congenital myopathy in which relative hypotrophy of type 1 (slow twitch) muscle fibers is the principal abnormality on histology. Second, we investigated an association between SEPN1-related myopathy and insulin resistance.
We sequenced SEPN1 in five unrelated CFTD patients with scoliosis and respiratory muscle weakness and screened an additional 22 CFTD patients for abnormalities in SEPN1 by Western blotting and restriction digest for the 943GA mutation. We performed oral glucose tolerance tests (OGTTs) in eight SEPN1-related myopathy patients.
Two sisters with CFTD were homozygous for the 943GA SEPN1 mutation and had clinical features typical of previously reported patients with SEPN1-related myopathy. Five of eight SEPN1-related myopathy patients had abnormalities on OGTT suggestive of insulin resistance.
SEPN1 is the second genetic cause of CFTD and the first cause of autosomal recessive CFTD to be identified to our knowledge. CFTD is the fourth clinicopathological presentation that can be associated with mutations in SEPN1. Insulin resistance may be a specific, previously unrecognized aspect of SEPN1-related myopathy. Ann Neurol 2006