The aim of this study was to analyze patients from two distinct families with a novel distal titinopathy phenotype associated with exactly the same CNV in the TTN gene. We used an integrated strategy combining deep phenotyping and complete molecular analyses in patients. The CNV is the most proximal out‐of‐frame TTN variant reported and leads to aberrant splicing transcripts leading to a frameshift. In this case, the dominant effect would be due to dominant‐negative and/or haploinsufficiency. Few CNV in TTN have been reported to date. Our data represent a novel phenotype–genotype association and provides hypotheses for its dominant effects.

Due to the widespread use of next generation sequencing (NGS), the titin gene (TTN) is emerging as a major causative gene in neuromuscular disorders, with high clinical heterogeneity. The mechanisms underlying the phenotypic variability and mode of inheritance recessive or dominant of titinopathies are poorly understood. They involve the primordial structural functions of the titin on the formation and stability of the sarcomere, as well as its interactions with other proteins. Effects of variants in TTN are variable, silent, recessive or dominant, and bioinformatics tools are not really efficient for interpretation of their functional impact, making them extremely difficult to interpret. Moreover, TTN variants are very frequent in the general population. Thus, expect the cases of recessive titinopathies due to compound heterozygous truncating variants, it is not possible to confirm whether the phenotype of a patient is due to a titinopathy, leaving patients without diagnosis. It is thus important to implement functional tests to evaluate the pathogenic effects of TTN variants, even truncating ones, on transcripts, titin quantity, size and functionality. We recently implemented titin western blot (WB) analysis, that was challenging due to the huge size of the protein. Our project is to perform, in patients with skeletal myopathy (with or without cardiomyopathy) and potentially disease causing TTN variant(s), an integrated genotype-transcrits-protein-heredity-phenotype approach. Our strategy will be to perform 1) complete collection of family, clinical and paraclinical data 2) exhaustive analysis of genotypic data 3) transcripts studies and WB of titin and interacting proteins 4) integrated analysis of all data and their comparison with published ones. We will present the first results. This integrated approach should improve patient diagnosis and knowledge of the molecular mechanisms underlying the variability of inheritance patterns and phenotypes.

Nemaline myopathy (NM) is a genetically heterogeneous congenital myopathy due to mutations in different encoding proteins. Mutations in the nebulin (NEB) gene are the most common cause of autosomal recessive NM. Typical NEB-related NM is of infantile-onset but late-onset presentations with predominantly distal involvement have been reported in very rare cases. We presented the clinical and histological phenotype of three patients manifesting with prominent distal weakness with bilateral foot-drop of adult onset associated with NEB gene mutations. One brother and his sister, aged of 49 and 42 years old respectively developed distal lower limbs weakness with foot drop from the age of 35. Initial clinical examination showed isolated tibialis anterior weakness but more recently the brother developed progressively finger extensor and neck flexors weakness. Myography showed a myogenic pattern. Whole body MRI showed selective involvement of tibialis anterior for both patients. Muscle biopsy was done in the sister showing dark blue structures with Gomori trichrome stain compatible with rods. Ultrastructural studies are currently ongoing. Next generation sequencing showed two variants in the nebulin gene in both patients: the frameshift c.8860delG and the missense c.21823 predicted to be pathogenic. The third patient was a male aged of 60 years old. He complained of walking difficulties from the age of 57. Neurologic examination showed isolated distal weakness of lower limbs mostly affecting tibialis anterior. Muscle biopsy showed blue structures with Gomori trichrome stain, but not typical rods. Electronic microscopy is ongoing. Next generation sequencing identified the presence of two missense variants in NEB gene: c.21790G > C, reported in 2006 by Lehtokari et al and c.2771A > C predicted to be pathogenic. In conclusion, we describe three patients with an adult onset distal myopathy secondary to recessive mutations in NEB gene expanding the phenotypic spectrum of NEB gene mutations.

L'importance de la mesure de la couleur du bois d'un arbre sur pied, abattu ou stocké sur le parc à bois, pour l'évaluation de sa qualité et de son prix, nous a amenés à développer la mesure de la couleur après prélèvement d'une carotte de sondage de 5 ou 10 mm de diamètre.La carotte de sondage, incluse dans un bloc de bois de hêtre, est ensuite tranchée en feuilles de placage mince (6/10" de mm) dans les conditions industrielles.Ces feuilles de placage, qui ont un état de surface comparable à celui des placages industriels obtenus à partir des mêmes billes de bois, servent à la mesure de la couleur à l'aide d'un spectrophotocolorimètre.Ces mesures permettront de connaître objectivement la couleur des arbres et de procéder à des comparaisons et des classements entre eux, dans les différents systèmes de mesure des écarts de couleur CIELAB ou HUNTER L, a, b.

Étude complémentaire sur l'influence de la fertilisation sur la qualité du

Dans une expérience portant sur 3 jeunes douglas, on a repéré dans l'espace ics limites de cernes successifs, à l'aide d'un système de coordonnées tri-rectangulaires, rapportées à un plan de sciage longitudinal, un plan perpendiculaire au premier et également parallèle au fil du bois, et une série de plans transversaux équidistants de 40 cm.On observe, par 2 méthodes de mesure différentes, une diminution de la flexuosité de la moelle vers l'écorce : en eutre, les cernes sont plus larges sur le rayon correspondant au côté comprimé, et il existe une corrélation très étroite entre l'excentricité et la pente du billon au-dessus du point de mesure.