normal intelligence, three have intellectual disability with ability to use some language and two are nonverbal. Age at presentation ranges from infancy to young adulthood. Three of the eight have epilepsy. None of the patients in this series has cardiomyopathy related to muscular dystrophy. Five patients have had brain MRIs, and two of these were abnormal, showing ventriculomegaly in both. Those with the most limited motor abilities have the most severe intellectual disability, epilepsy and earliest age at onset of weakness (infancy). Review of the mutations found in our eight families together with the fifteen previously published families with GMPPB mutations, led to identification of two common mutations. We suggest that they are associated with consistent clinical phenotypes, although additional patients will be required to confirm this observation. http://dx.doi.org/10.1016/j.nmd.2015.06.300 G.P.277 Diagnostic difficulties in muscular dystrophy due to LAMA2 mutations –A case report of affected father and his son J. Haberlová * ,1 , R. Barresi 2 , L. Fajkusová 3 1 Charles University, Child Neurology Department, Prague, Czech Republic; 2 Newcastle University, John Walton Muscular Dystrophy Research Centre, Newcastle, UK; 3 Faculty Hospital Brno, Centre of Molecular Biology and Gene Therapy, Brno, Czech Republic Congenital muscular dystrophies (CMD) are characterized by early onset hypotonia and muscle weakness along with a dystrophic pattern in muscle biopsy. They are rare diseases with great heterogeneity, which makes the diagnosis difficult. CMD, due to LAMA2 mutations, are one of the most frequent forms of CMD. The authors present a family with an affected father and his son. They both noticed the first symptoms of muscle weakness between the age of 6 and 8 years. The muscle weakness had limb girdle maximum with mild facial weakness. They both had developed the contractures of Achilles tendons. The progression is very mild; the father uses crutches when walking at the age of 64 years, the boy is able to walk independently and had difficulty in running at the age of 12 years. The son has mildly elevated CK 18 µkat/l (6× upper limit) and myoglobin 180 µg/l (3× upper limit); the father has normal values. The father underwent muscle biopsy that revealed a mild myopathic pattern with increased interstitial fibrosis. The immunohistochemical staining (laminin α2 included) was normal. Later, due to a head injury, the son had a brain MR that revealed leukodystrophic changes. The genetic testing by sequence capture and targeted resequencing of 42 genes associated with neuromuscular disorders of both patients found two possible causal novel gene variants – one in DNM2 gene (p.Asp215Asn) and the second in LAMA2 gene [father c.799G > A/c.9095dupA – p.(Asp267Asn)/p.(Ile3033Aspfs*6), son c.799G > A/c.3691G > T – p.(Asp267Asn)/p.(Glu1231*)]. Due to MR changes the immunohistochemical staining with other two laminin α2 antibodies (80/ 300 kDa) was added and confirmed the diagnosis of partial laminin α2 deficiency. For diagnosis of partial merosin deficiency it is essential to use more than one antibody against merosin. The initially considered myopathy with AD inherited pattern finally occurs to be AR. http://dx.doi.org/10.1016/j.nmd.2015.06.301 G.P.278 Next generation sequencing (NGS):A powerful tool for studying rigid spine patients and multiminicore myopathy J. Gurgel-Giannetti * ,1 , E. Concentino 1 , M. Lazar 2 , V. Van der Linden 3 , A. Giannetti 4 , F. Fernandes 1 , W. Campos 5 , M. Vainzof 2 1 Federal University of Minas Gerais, Medical School – Pediatrics, Belo Horizonte, Brazil; 2 University of São Paulo, Centro de Estudos do Genoma Humano, São Paulo, Brazil; 3 AACD, Pediatric Neurology, Recife, Brazil; 4 Federal University of Minas Gerais, Surgery, Belo Horizonte, Brazil; 5 Federal University of Minas Gerais, Radiology, Belo Horizonte, Brazil The selenoprotein N gene (SEPN1) is related to the different forms of myopathies including dystrophy with rigid spine (MDRS), multiminicore myopathy, myopathy with fiber type disproportion, myopathy associated with desmin accumulation and myopathy with inclusion type Mallory body. We evaluated the presence of SEPN1 mutations in Brazilian patients with these phenotypes using Sanger and next generation sequencing (NGS). Patients with myopathy related to SEPN1 were submitted to clinical evaluation, CK, ENMG, muscle biopsy with histochemistry and muscle MRI analyses. DNA study was performed through SANGER sequencing for the SEPN1 gene and using a next generation sequencing customized panel for 88 genes involved in neuromuscular disorders (Illumina). We evaluated twelve patients from ten unrelated families: 8 were classified with MDRS, 3 patients with myopathy multiminicore and one patient with congenital fiber disproportion. The molecular analysis revealed pathogenic SEPN1 mutations in 4 families (c.T1384G, c.713-14insA, c.1406G > A, c.1397G > A and a novel c.G1010T). In patient 1 who was heterozygous compound for c. T1384G and the novel c. G1010T mutations, the muscle MRI showed changes compatible with the pattern of SEPN1. Other patients with congenital disproportion fiber showed insertion of 12 bases in phase (c316-317 Ins.12 bp) in exon 1 of the SEPN1 gene, which pathogenicity is not clear. One patient with rigid spine phenotype showed a known mutation in the COL6A1 gene. A second one with multiminicore myopathy was a compound heterozygous for 2 novel germline mutations in the COL6A3 gene. Myopathies related to selenoprotein N have a broad clinical phenotype and histology. Also, the rigid spine phenotype and multiminicore myopathy can be related to different genes. The use of NGS panel could confirm mutations in SEPN1 (4 patients) and also was helpful for identifying mutations in other neuromuscular genes. http://dx.doi.org/10.1016/j.nmd.2015.06.302 G.P.279 Congenital muscular dystrophies in the UK population: Update of clinical and molecular spectrum of patients diagnosed over a 12-year period M. Sframeli * ,1 , A. Sarkozy 1 , M. Bertoli 2 , G. Astrea 3 , J. Hudson 2 , M. Scoto 1 , R. Mein 4 , M. Yau 4 , R. Phadke 1 , L. Feng 1 , C. Sewry 1 , S. Robb 1 , A. Manzur 1 , S. Messina 5 , K. Bushby 2 , F. Muntoni 1 1 Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK; 2 The John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, University of Newcastle, Central Parkway, Newcastle upon Tyne, UK; 3 Neuromuscular and Molecular Medicine Unit, Department of Developmental Neuroscience, IRCCS Stella Maris, Pisa, Italy; 4 DNA Laboratory, GSTS Pathology, Genetics Centre, Guy’s Hospital, London, UK; 5 Department of Neurosciences and NEMO SUD Clinical Centre, Messina, Italy Congenital muscular dystrophies (CMDs) are a heterogeneous group of conditions; some fatal in the first few years of life and associated with central nervous system involvement, whereas others with a milder course. We report the relative frequency and clinical and genetic spectrum of CMDs in the UK patients for whom genetic analysis of the CMD genes was requested between 2001 and 2013. In this time frame, the two UK centres performing genetic analysis of CMD genes, the Dubowitz Neuromuscular Centre (DNC), the national referral centre for diagnosis and assessment of CMDs in London, and the NCST Diagnostic & Advisory Service for Limb girdle muscular dystrophies in Newcastle, received a total of 3734 referrals. Overall 1042 patients were referred to the DNC for LAMA2, POMT1, POMT2, POMGNT1, FKRP, FKTN, LARGE, ISPD, GMPPB, B3GALNT2, COL6A1, COL6A2, COL6A3 and SEPN1 genetic testing; while 2692 referrals for LMNA and FKRP genetic testing were made to the NSCT centre in Newcastle. A confirmed genetic diagnosis was reached in 441 families (12%). Detailed clinical information was available for 419 patients; 250 fulfilled a clinical diagnosis of CMD while the other 169 had milder allelic conditions. The most common type of genetically confirmed CMD was laminin-α2 related CMD (MDC1A) accounting for 37.2% of cases, followed by dystroglycanopathies (26.4%), Ullrich-CMD (15%), CMD related to mutations in SEPN1 (11.6%) and LMNA S269 Abstracts/Neuromuscular Disorders 25 (2015) S184–S316