study, we searched for LMNA mutations in 94 unrelated patients patho- logically diagnosed as CFTD. Genetically confirmed 29 LMNA-myopathy patients were also reevaluated pathologically. We identified two patients carrying a novel heterozygous LMNA mutation (p.Glu33del or p.Lys123- del) among 94 CFTD patients. On the other hand, 5 of 29 (17%) LMNA- myopathy patients showed fiber type disproportion (FTD) on muscle pathology. The age at onset of the 7 LMNA-myopathy patients with FTD was from 1y2m to 4y (mean 2y8m) except for one adult-onset patient. None of the LMNA-myopathy patients with FTD had high arched palate or respiratory involvement. Serum creatine kinase levels were mildly elevated (mean 915h} 698 IU/L). The ratio of fiber size dis- proportion (%FSD) was not significantly different between LMNA-myop- athy withFTD and 9 CFTD patients with ACTA1 or TPM3 mutations. Importantly, CFTD with ACTA1 or TPM3 mutations showed type 1 fiber atrophy compared to age-matched controls, while LMNA-myopathy with FTD showed type 2 fiber hypertrophy. From our results, we encourage LMNA mutation analysis in CFTD patients with no high arched palate and respiratory involvement. http://dx.doi:10.1016/j.nmd.2012.06.330 RARE MYOPATHIES AND EXPERIMENTAL APPROACHES - POSTER PRESENTATIONS G.P.125 ACTN3 genotype influences skeletal muscle performance through alterations in calcineurin signaling K.G.R. Quinlan 1 , J.T.C. Seto 2 , M. Lek 2 , F.X. Zheng 2 , F. Garton 2 , P.J. Houweling 2 , K.N. North 2 1 University of Sydney, Institute for Neuroscience and Muscle Research, Sydney, Australia; 2 The Children’s Hospital at Westmead, Institute for Neuroscience and Muscle Research, Sydney, Australia Approximately 1 billion people worldwide do not express the fast- twitch skeletal muscle fibre protein alpha-actinin-3 (a-act-3) due to homo- zygosity for a common null polymorphism in the ACTN3 gene. ACTN3 genotype influences skeletal muscle performance in elite athletes and in the general population; a-act-3 deficiency is associated with enhanced endurance capacity. Studies of the Actn3 KO mouse revealed that a-act- 3 deficiency leads to a shift in fast muscle fibre contractile and metabolic properties towards those normally associated with slower muscle fibres. To gain mechanistic insights into these changes we performed a micro- array and, interestingly, found that downstream targets of the calcineurin signalling pathway are altered in a-act-3 deficient muscle. We have now shown that the activity of calcineurin, which plays a critical role promot- ing fast-to-slow twitch fibre transition, is increased in KO mouse muscle, which likely accounts for the enhanced endurance performance in KO mice. We hypothesised that, due to the increased calcineurin activity, a- act-3 deficient muscle, may more readily adapt to physical demands that result in a fast-to-slow fibre conversion. KO mice demonstrate greater improvements in endurance performance following forced treadmill endurance training, associated with greater shifts in fast to slow fibre tran- sition, increased fibre size and higher oxidative muscle metabolism com- pared to WT. We demonstrate that alpha-actinin-2 (a-act-2), which is upregulated in a-act-3 deficient muscle, has increased binding affinity for calsarcin-2, a key inhibitor of calcineurin activity. a-Act-2 competes with calsarcin-2 for binding to calcineurin, resulting in enhanced calcineurin signaling and the activation of the slow myogenic program. Our data pro- vide, for the first time, a mechanistic explanation for the effects of ACTN3 genotype on skeletal muscle performance in elite athletes and adaptation to changing physical demands in the general population. http://dx.doi:10.1016/j.nmd.2012.06.331 G.P.126 “Strongman syndrome”: A new autosomal dominant herculean painful myopathy N. Al-Bustani 1 , M. Te ´treault 2 , S. Provost 3 , V. Bolduc 4 , M. Srour 5 , E.K. O’Ferrall 1 , M.P. Dube ´ 3 , J.P. Bouchard 6 , G. Ravenscroft 7 , D. Bignell 7 , N.G. Laing 7 , P.J. Lamont 8 , J. Mathieu 9 , B. Brais 2 1 McGill University Health Center, Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Canada; 2 McGill University, Universite ´ de Montre ´al, Neurogenetics of Motion Laboratory, Montreal Neurological Institute, CHUM Research Center, Notre-Dame Hospital, Montreal, Canada; 3 Universite ´ de Montre ´al, StatGen, Statistical Genetics Research Group, Montreal Heart Institute, Montreal, Canada; 4 Universite ´ de Montre ´al, CHUM Research Center, Notre-Dame Hospital, Montreal, Canada; 5 McGill University Health Centre, Universite ´ de Montre ´al, Department of Neurology, The Montreal Children’s Hospital, CHUM Research Center, Notre-Dame Hospital, CHU Sainte-Justine Hospita, Montreal, Canada; 6 Universite ´ Laval, De ´partement des sciences neurolog- iques, CHUQ – Ho ˆ pital de l’Enfant-Je ´sus, Quebec, Canada; 7 Center for Medical Research, The University of Western Australia, Western Australian Institute for Research, Nedlands, Australia; 8 Royal Perth Hospital, Department of Neurology, Perth, Western Australia, Australia; 9 Clinique des Maladies neuromusculaires, CSSS de Jonquie `re, Quebec, Canada The objective was to define clinical criteria for a novel autosomal dom- inant (AD) herculean painful myopathy. We reviewed the clinical assess- ment of 74 cases that presented with myalgia, muscle cramps, increased muscle bulk, above normal strength with a negative electrophysiological and genetic workup. We evaluated 42 members of the largest family and defined a clinical scale to establish affection status. Review of the 74 cases demonstrated the majority had a positive family history. The larger fam- ilies support AD transmission with a variable phenotype. Cases presented with combinations of the following major symptoms and signs: above average strength, myalgia post-activity, deltoid fatigability after repeated contractions and percussion pseudomyotonia in more than two limbs. Many also presented with some of the following minor findings: poor quality sleep, excessive movements at night, weakness after repetitive movements, very large muscle bulk, calf hypertrophy, well defined mus- cles, clear superior strength by confrontation and proximal weakness affecting the iliopsoas. By doubling the weight given to the major findings we developed a 20-point affection scale. In the largest family this con- firmed AD transmission. Few cases had elevated serum CPK levels. None had electrical myotonia, or decremental response on EMG. Muscle biop- sies were unremarkable. Mutations in MYSN were excluded in 13 cases. No mutations were found in CAV3, CLCN1 or SCN4A. Though weak- ness after repeated contractions was common, none tested had electro- physiological evidence of myasthenia, nor DOK7 mutations. In some older cases a proximal weakness developed such that the condition evolved into a late-onset LGMD. We have identified a large number of Canadian and Australian cases affected by a variably painful herculean myopathy apparently transmitted in an AD fashion. Further genetic characterization of the larger families should uncover candidate loci and gene. http://dx.doi:10.1016/j.nmd.2012.06.332 G.P.127 A nation-wide survey for Marinesco-Sjo ¨gren syndrome M. Goto 1 , Y.K. Hayashi 2 , M. Okada 2 , H. Komaki 3 , K. Sugai 3 , M. Sasaki 3 , S. Noguchi 2 , I. Nonaka 2 , I. Nishino 2 1 National Center Hospital, National Center of Neurology, and Psychiatry, Child Neurology, Kodaira, Japan; 2 National Institute of Neuroscience, Neuromuscular Research, Kodaira, Japan; 3 National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Child Neurology, Kodaira, Japan 904 Abstracts / Neuromuscular Disorders 22 (2012) 804–908