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.
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 CFTDpatients with scoliosis and respiratory muscle weakness and screened an additional 22 CFTDpatients 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 myopathypatients. 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 myopathypatients 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.
Authors: Cristina Dias; Murat Sincan; Praveen F Cherukuri; Rosemarie Rupps; Yan Huang; Hannah Briemberg; Kathryn Selby; James C Mullikin; Thomas C Markello; David R Adams; William A Gahl; Cornelius F Boerkoel Journal: Hum Mutat Date: 2012-02-28 Impact factor: 4.878
Authors: Nigel G Laing; Danielle E Dye; Carina Wallgren-Pettersson; Gabriele Richard; Nicole Monnier; Suzanne Lillis; Thomas L Winder; Hanns Lochmüller; Claudio Graziano; Stella Mitrani-Rosenbaum; Darren Twomey; John C Sparrow; Alan H Beggs; Kristen J Nowak Journal: Hum Mutat Date: 2009-09 Impact factor: 4.878
Authors: Behzad Moghadaszadeh; Branden E Rider; Michael W Lawlor; Martin K Childers; Robert W Grange; Kushagra Gupta; Steve S Boukedes; Caroline A Owen; Alan H Beggs Journal: FASEB J Date: 2013-01-16 Impact factor: 5.191
Authors: Michael W Lawlor; Elizabeth T Dechene; Emily Roumm; Amelia S Geggel; Behzad Moghadaszadeh; Alan H Beggs Journal: Hum Mutat Date: 2010-02 Impact factor: 4.878