Italy; c Center of Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany; d Biologia Cellulare Muscoloscheletrica, IOR, Bologna, Italy We have defined the expression and localization of the two novel col- lagen type VI chains, alpha5 and alpha6, in normal muscle tissue and cul- tures. In muscle sections, the alpha6 chain was detected in the endomysium and perimysium, while the alpha5 chain was restricted to the myotendinous junctions. In muscle cultures, the alpha5 chain was absent while the alpha6 was present in traces in the ECM; the treatment with pro-fibrotic factor TGF-beta1 did not affect the expression of alpha5 chain, while, the alpha6 chain was markedly increased. In order to define the involvement of alpha6 chain in muscle fibrosis we studied biopsies of patients affected by Duchenne Muscular Dystrophy (DMD) and Congen- ital Muscular Dystrophy 1A (MDC1A). We found that alpha6 chain was dramatically up-regulated in fibrotic areas where, in contrast, the alpha5 chain was undetectable. Our data indicate a differential distribution of alpha5 and alpha6 chains in skeletal muscle; while the alpha5 chain may have a specialized function in areas of tissues subjected to tensile stress, the alpha6 chain appears to be involved in (and/or contributes to) ECM remodeling upon fibrosis. doi:10.1016/j.nmd.2011.06.830 P2.8 Congenital muscular dystrophy with intracytoplasmatic aggregates on muscle biopsy caused by mutation on LMNA gene L.M. Pasqualin, E. Zanoteli, M.A.V. Albuquerque, C.A. Martins, O.L.A. Neto, M.B.D. Resende, G. Chadi, U.C. Reed University of Sa ˜ o Paulo, Department of Neurology, Sa ˜ o Paulo, Brazil Congenital Muscular Dystrophy (CMD) is a heterogeneous group of myopathies with dystrophic features on muscle biopsy and weakness, hypotonia, joint contractures and delayed motor development from the first months of life. Recently, patients with a CMD phenotype character- ized by marked neck weakness were identified in association with muta- tions on LMNA gene that codifies the A/C lamin. So far the most common myopathic phenotypes associated to the A/C lamin deficiency were the dominant autossomal form of Emery-Dreifuss muscular dystro- phy (ED) and type 1B limb girdle muscular dystrophy (LGMD1B). A de novo heterozygous mutation (E358K) in exon 6 of LMNA gene was iden- tified in a 9-y-old boy with delayed motor milestones, weakness of proxi- mal portion of the limbs and neck muscles (especially for extension of the neck), and progressive worsening of weakness and osteoskeletal deformi- ties. The muscle biopsy showed a mild dystrophic pattern with a marked presence of intracytoplasmic aggregates. Immunostaing for merosin, dys- trophin, collagen VI, sarcoglycans, dysferlin, caveolin-3, emerin and A/C lamin proteins were normal. The mutation identified in this patient has been previously described in patients with “dropped head” CMD and also in ED or LGMD phenotype. This report confirms previous observations that the same mutation in the LMNA gene can be associated with a wide spectrum of conditions ranging from a moderate phenotype like in ED and LGMD to a more severe disease like in CMD with dropped head (Sponsored by FAPESP no. 2010/08902-5). doi:10.1016/j.nmd.2011.06.831 P2.9 LMNA-related congenital muscular dystrophy: Clinical, pathological and molecular findings M.S. Monges a , F. Lubieniecki b , S. Quijano-Roy c , M. Saccoliti d , N.B. Romero e , P. Richard f , A.L. Taratuto d a Garrahan National Paediatric Hospital, Department of Neuropaediatrics, Buenos Aires, Argentina; b Garrahan National Paediatric Hospital, Depart- ment of Pathology, Buenos Aires, Argentina; c Ho ˆ pital Universitaire Raymond Poincare ´, Centre National de Re ´fe ´rence des Maladies Neurom- usculaires Garches-Necker-Mondor-Hendaye, Service de Pe ´diatrie, Garch- es, France; d FLENI Institute for Neurological Research, Department of Neuropathology, Buenos Aires, Argentina; e Institut de Myologie, Centre de Re ´fe ´rence Neuromusculaire Paris-Est, GHU Pitie ´-Salpe ˆtrie `re, UPMC Paris 6, UMR S974, INSERM U974, CNRS UMR 7215, Paris, France; f GHU Pitie ´ Salpetriere, UF de Cardiogenetique et Myogenetique Moleculaire et Cellulaire, Paris, France Since first recognized as an entity by Quijano et al. in 2008, there are only few reports of patients with LMNA-related congenital muscular dys- trophy (L-CMD).We describe three patients with L-CMD. (1) Two-year- 10-month-old girl with generalized hypotonia and weakness since birth, developed hyperlordosis and head drop. CK 991 IU/l. Deltoid-muscle biopsy resembled SMA rather than CMD. Ultrastructural study showed abnormal nuclei: invagination, fragmentation, pseudoinclusions. Molecu- lar studies ruled out SMN but identified a heterozygous missense mutation p.Arg249Trp (C.745 C > T) exon 4. (2) Six-year-old male had progressive hyperlordosis and head drop since 11 months of age as well as loss of deam- bulation and proximal-upper-limb and distal-lower-limb hypotrophy at 15 months, requiring non-invasive ventilation since 5 yrs. CK 841 IU/ l.Deltoid-muscle biopsy showed a dystrophic pattern, increase of central nuclei, and central focal oxidative activity in some fascicles. Molecular studies showed a Lys32Glu (K32E) heterozygous missense mutation in exon 1. (3) Six-year-old male who had generalized weakness and proxi- mal-upper-limb hypotrophy, frequent falls, and head drop since 1 yr of age. CK 937 IU/l. Deltoid-muscle biopsy showed a relatively preserved structure with perimysial fibrosis, one necrotic fiber, and increased oxida- tive central activity in some fascicles. Ultrastructural study showed abnor- mal nuclei: fragmentation, invagination, and folding membrane. Molecular studies identified a heterozygous missense mutation p.Thr528Arg (c.1583 C > G) exon 9. None of our patients showed cardiac involvement or elbow contractures. Mutations of the LMNA gene are responsible for a heteroge- neous group of diseases including L-CMD. We found that, regardless of the biopsy findings, proximal upper-limb and distal lower limb hypotrophy and weakness with a drop head in a child with slight increase of CK should prompt molecular genetic analysis of LMNA. doi:10.1016/j.nmd.2011.06.832 P2.10 A new form of congenital muscular dystrophy with subsarcolemmal inclu- sions arising from disintegrated myonuclei A.L. Taratuto a , I. Nelson b , M. Olive ´ c , H. Waisburg d , M. Saccoliti a , M. Beuvin b , D. Chauveau e , P. Richard f , T. Voit b , G. Bonne b , N.B. Romero b a FLENI Institute for Neurological Research, Department of Neuropathol- ogy, Buenos Aires, Argentina; b UPMC Paris 6, UM 76, INSERM U974, CNRS UMR 7215, Institut de Myologie, GHU Pitie ´-Salpe ˆtrie `re, Paris, France; c Unite ´ de Morphologie Neuromusculaire, Institut de Myologie, GHU Pitie ´ -Salpe ˆtrie `re, Paris, France; d Garrahan National Paediatric Hospital, Department of Neuropaediatrics, Buenos Aires, Argentina; e Unite ´ de Morphologie Neuromusculaire, Institut de Myologie, GHU Pitie ´- Salpe ˆtrie `re, Centre de re ´fe ´rence des maladies neuromusculaires Paris-Est, Paris, France; f AP-HP, U.F. Cardioge ´ne ´tique et Myoge ´ne ´tique, Service de Biochimie Me ´ tabolique, Groupe Hospitalier Pitie ´-Salpe ˆtrie ` re, Paris, France Abnormalities in muscle nuclei have been described in several disorders including emerinopathies, laminopathies, Marinesco-Sjo ¨ gren syndrome and isolated genetically still unresolved cases. A 4 year-old girl was referred at the age of 16 months due to delayed motor development. She was the second child of healthy unrelated parents. She was born by normal delivery after an uneventful pregnancy at 39 weeks of gestation. She was hypotonic at birth and developed severe respiratory distress requiring nasal oxygen therapy. Investigations for cardiac, brain and kidney Abstracts / Neuromuscular Disorders 21 (2011) 639–751 663