100%-mutant transmitochondrial hybrid mitochondria showed that only 20–25% of the holocomplex was fully assembled. Our findings add a novel etiology to the heterogeneous presentation of MELAS. doi:10.1016/j.nmd.2007.06.029 M.P.1.05 The COII/tRNALys intergenic 9-bp deletion in mtDNA: A new possible cause of sensorineural hearing loss? Castello, F. * ; Borgione, E.; Musumeci, S.; Rizzo, G.; Elia, M.; Calabrese, G.; Scuderi, C. Associazione OASI Maria SS, Troina, Italy A deletion of one of the two copies of the intergenic 9-bp repeat sequence (CCCCCTCTA), located between the cytochrome oxidase II and lysine tRNA genes of mitochondrial DNA, has previously been used as a polymorphic anthropological marker (MIC9D) for people of east Asian origin, and – to a lesser extent – in Oceanian and African popula- tions. Although this polymorphism is common in Africa and Asia, it has not been reported in Northern Europe. We report the presence of the 9-bp deletion, identified by RFLP and confirmed by sequence analysis, in homoplasmy in lymphocytes of four patients (one proband and his mother, two other unrelated females) with sensorineural hearing loss and variable neurological signs such as mental retardation, epilepsy, reti- nitis pigmentosa and myopathy. This deletion was absent in 100 Cauca- sian controls. Although additional evidence is needed, our results suggest that the MIC9D polymorphism may play a pathogenetic role in some ethnies. doi:10.1016/j.nmd.2007.06.030 M.P.1.06 A novel mutation in the mitochondrial ND3 gene causing Leigh syndrome with late-onset neurological decline Tchikviladze ´, M. 1,* ; Lafore ˆt, P. 2 ; Eymard, B. 3 ; Delbos, F. 4 ; Filaut, S. 4 ; Lombe `s, A. 5 ; Jardel, C. 6 1 Institut de Myologie,APHP, Pitie ´-Salpe ˆtrie `re, Service de Neurology Mazarin, Paris, France; 2 Institut de Myologie, Pitie ´-Salpe ˆtrie ` re,APHP, Neurology, Paris, France; 3 Institut de Myologie, APHP, Pitie ´-Salpe ˆtrie `re, Neurology, Paris, France; 4 APHP,Pitie ´ -Salpe ´trie `re, Biochimie, UF de Cardioge ´ne ´tique et Myoge ´ne ´tique, Paris, France; 5 INSERM U582, Paris, France; 6 APHP,Pitie ´-Salpe ´trie `re, UF de Cardioge ´ne ´tique et Myoge ´ne ´- tique, Paris, France Leigh syndrome (LS) is a subacute necrotizing encephalomyopathy occurring most often in childhood, and frequently associated with com- plex I deficiency. Recently, a novel mutation m.10197G > A in mitochon- drial (mt) DNA-encoded complex I subunit gene ND3 was identified in young children of three unrelated families with LS and dystonia. We report here the observation of an adult patient with LS harbouring the same mutation. A 30-year-old man presented at the age of 6 years, with bilateral optic atrophy and horizontal nystagmus. These signs remained stable until the age of 30 when the patient developed a subacute neurolog- ical disorder with dysarthria, ophthalmoplegia, and dystonic gait, con- comitant with thyrotoxicosis. A partial reversal of the neurological symptoms occurred after treatment of hyperthyroidism, followed by a progressive worsening/decline in the following years. Brain MRI showed bilateral brainstem lesions. CSF and serum lactate concentrations were normal. Histochemical studies performed on skeletal muscle were unre- markable, but the measurement of the respiratory chain complexes activ- ities showed an isolated defect in complex I. Subsequent analysis of the mt DNA revealed a m.10197G > A mutation in the MT-ND3 gene, resulting in a substitution of hydrophobic alanine to hydrophilic threonine in the highly conserved amino acid 47. Mutant mtDNA was present at different levels of heteroplasmy in all studied tissues: muscle (100%), buccal mucosa cells (70%) and leucocytes less than 50%. In conclusion, we report the first case of severe adult LS due to a mutation in MT-ND3 gene with late-onset and severe neurological decline. This neurological severity is not usual with a low amount of blood mutated DNA. The influence of thyroid dys- function cannot be excluded as worsening factor of the neurological status of the patient. Moreover, this report suggests that mt DNA complex I genes are candidate genes for Leigh syndrome in adults as it is the case in children. doi:10.1016/j.nmd.2007.06.031 M.P.1.07 Detection of single mtDNA deletions by Long-Range-PCR in blood of patients with CPEO Wendt, M. 1,* ; Taylor, R. 2 ; Rokicka, A. 1 ; Zierz, S. 1 ; Deschauer, M. 1 1 University of Halle-Wittenberg, Neurology, Halle, Germany; 2 Newcastle University, School of Neurology, Neurobiology and Psychiatry, Newcastle upon Tyne, United Kingdom Introduction: Chronic progressive external ophthalmoplegia (CPEO) can present with different multisystemic involvement. Kearns–Sayre-syn- drome (KSS) is a severe multisystemic phenotype characterized by CPEO with retinopathy, onset of disease before age 20, and heart block, cerebel- lar ataxia or elevated protein in cerebrospinal fluid. But there is doubt on the nosological entity of KSS. Deletions of mitochondrial DNA (mtDNA) can be identified by Southern blot analysis in CPEO and KSS in muscle. However, it was postulated that in blood deletions are only detectable in KSS but not in CPEO. Methods: We examined 27 patients with CPEO and different multisystemic involvement in whom a single mtDNA deletion in muscle was identified by Southern blot analysis. For more sensitive detec- tion of mtDNA deletions Long-Range-PCR analysis using DNA from muscle and blood was performed with different elongation times. Results: Three patients fulfilled the criteria of KSS. In all patients the deletion was detectable by Long-Range-PCR using muscle DNA. Southern blot analy- sis detected the deletion in blood in one patient only. In 13/27 patients we have identified the deletion by Long-Range-PCR in blood. Sensitivity increased with reduction of elongation time. However, very short deletions were not picked up by a short elongation time. Deletions were present in blood in 2 patients with KSS and in 11 patients with CPEO. Discussion: Detection of mtDNA deletions in blood is not specific for KSS. Deletions were not detectable in all patients with KSS and they are also found in blood of patients with CPEO. Sensitivity of Long-Range-PCR analysis increases with reduction of the elongation time. Long-Range-PCR analy- sis is more sensitive than Southern blot analysis and is easier to perform. Deletions of mtDNA are detectable in blood in half of the patients with CPEO due to single mtDNA deletions. Our data support the assumption that KSS is not a nosological entity but a severe form of CPEO. doi:10.1016/j.nmd.2007.06.032 M.P.1.08 A novel mutation in the mitochondrial tRNA LeuCUN gene associated with a mitochondrial myopathy with respiratory impairment Virgilio, R. 1,* ; Bordoni, A. 2 ; Ronchi, D. 2 ; Saladino, F. 2 ; Bresolin, N. 2 ; Sciacco, M. 2 ; Comi, G. 2 1 IRCSS Ospedale Maggiore-University of Milano, Department of Neuro- science, Milano, Italy; 2 Department of Neuroscience-IRCCS Ospedale Maggiore-University of Milano, Department of Neuroscience, Milan, Italy Mutations in mitochondrially encoded tRNA genes have been described in a variety of neurological disorders. Predominant phenotypes Abstracts / Neuromuscular Disorders 17 (2007) 764–900 769