OBJECTIVE: To describe two symptomatic dysferlin gene mutation carriers. METHODS: One patient had limb girdle weakness. His brother was diagnosed with limb girdle muscular dystrophy 2B with two mutations in the dysferlin gene (D625Y and E1734G). The second patient had distal weakness. He had two sons with Miyoshi myopathy with a homozygous mutation (G519R). We performed immunofluorescence (dystrophin, DAG proteins, dysferlin, caveolin-3), Western blot (dysferlin, caveolin-3, calpain-3), and real-time PCR (dysferlin) using skeletal muscle samples. We also studied dysferlin in peripheral blood monocytes (PBMs) by Western blot. RESULTS: In addition to the muscle weakness, both patients showed elevated creatine kinase and abnormal muscle MRI. They presented a mutation in only one allele after screening of the whole gene (skeletal muscle and monocyte mRNA and genomic DNA). A muscle biopsy specimen showed moderate dystrophic changes and patchy dysferlin expression in the sarcolemma. Western blot of both PBMs and skeletal muscle demonstrated a significant reduction in dysferlin. All the other proteins including caveolin-3 and calpain-3 were normal. Real-time PCR showed normal levels of dysferlin mRNA vs the patients' affected relatives. CONCLUSIONS: The diagnosis of symptomatic carriers of dysferlin mutations should be considered when a pathologic pattern of dysferlin protein is observed.
OBJECTIVE: To describe two symptomatic dysferlin gene mutation carriers. METHODS: One patient had limb girdle weakness. His brother was diagnosed with limb girdle muscular dystrophy 2B with two mutations in the dysferlin gene (D625Y and E1734G). The second patient had distal weakness. He had two sons with Miyoshi myopathy with a homozygous mutation (G519R). We performed immunofluorescence (dystrophin, DAG proteins, dysferlin, caveolin-3), Western blot (dysferlin, caveolin-3, calpain-3), and real-time PCR (dysferlin) using skeletal muscle samples. We also studied dysferlin in peripheral blood monocytes (PBMs) by Western blot. RESULTS: In addition to the muscle weakness, both patients showed elevated creatine kinase and abnormal muscle MRI. They presented a mutation in only one allele after screening of the whole gene (skeletal muscle and monocyte mRNA and genomic DNA). A muscle biopsy specimen showed moderate dystrophic changes and patchy dysferlin expression in the sarcolemma. Western blot of both PBMs and skeletal muscle demonstrated a significant reduction in dysferlin. All the other proteins including caveolin-3 and calpain-3 were normal. Real-time PCR showed normal levels of dysferlin mRNA vs the patients' affected relatives. CONCLUSIONS: The diagnosis of symptomatic carriers of dysferlin mutations should be considered when a pathologic pattern of dysferlin protein is observed.
Authors: Steven E Boyden; Anna R Duncan; Elicia A Estrella; Hart G W Lidov; Lane J Mahoney; Jonathan S Katz; Louis M Kunkel; Peter B Kang Journal: BMC Med Genet Date: 2011-06-28 Impact factor: 2.103
Authors: Alisdair McNeill; Daniel Birchall; Volker Straub; Lev Goldfarb; Peter Reilich; Maggie C Walter; Nicolai Schramm; Hanns Lochmüller; Patrick F Chinnery Journal: Eur Neurol Date: 2009-07-03 Impact factor: 1.710
Authors: J Díaz-Manera; T Touvier; A Dellavalle; R Tonlorenzi; F S Tedesco; G Messina; M Meregalli; C Navarro; L Perani; C Bonfanti; I Illa; Y Torrente; G Cossu Journal: Cell Death Dis Date: 2010-08-05 Impact factor: 8.469
Authors: Eduard Gallardo; Noemi de Luna; Jordi Diaz-Manera; Ricardo Rojas-García; Lidia Gonzalez-Quereda; Bàrbara Flix; Antoine de Morrée; Silvère van der Maarel; Isabel Illa Journal: PLoS One Date: 2011-12-16 Impact factor: 3.240