SEPN1: Associated with congenital fiber‐type disproportion and insulin resistance
NF Clarke, W Kidson, S Quijano‐Roy… - Annals of …, 2006 - Wiley Online Library
NF Clarke, W Kidson, S Quijano‐Roy, B Estournet, A Ferreiro, P Guicheney, JI Manson…
Annals of neurology, 2006•Wiley Online LibraryObjective 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. Methods We sequenced SEPN1 in five unrelated CFTD patients with
scoliosis and respiratory muscle weakness and screened an additional 22 CFTD patients for …
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. Methods We sequenced SEPN1 in five unrelated CFTD patients with
scoliosis and respiratory muscle weakness and screened an additional 22 CFTD patients for …
Objective
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.
Methods
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 943G→A mutation. We performed oral glucose tolerance tests (OGTTs) in eight SEPN1‐related myopathy patients.
Results
Two sisters with CFTD were homozygous for the 943G→A 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.
Interpretation
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
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