My scientific work has been built in parallel with my clinical activities as a neurologist and histopathologist in the field of rare neuromuscular diseases. I have mainly developed research on congenital myopathies and metabolic myopathies which are two groups of genetic diseases of growing interest for two main reasons: 1) the understanding of their physiopathological mechanisms allows to improve the scientific knowledge of muscle physiology, and 2) several therapeutic possibilities are opening up, acting either on enzymatic activities or through gene therapy approaches. My research has been possible thanks to the numerous cohorts of patients and notably muscle biopsies with rare congenital and metabolic myopathies that I have contributed to the study and discovery of new muscle diseases. Two categories of myopathies are the subject of my studies: metabolic myopathies, in particular muscle glycogenosis, and congenital myopathies. In recent years, I have been involved in the discovery of nine new genes and phenotypes of congenital myopathies (LMOD3, MYO18B, MYPN, PYRODXD1, ZAK, DHPR1, STAC3, ACTN2) and muscle glycogenosis (glycogenin 1, GYG1, myopathy with polyglucosan). In addition, I have contributed to the fine muscle morphological characterization of different forms of early myopathies contributing to the understanding of pathological mechanisms. In this respect, I have used a systematic integrated approach including deep clinical phenotyping, optical microscopy and ultracructural analysis. Thanks to my postdoc/mobility and a close collaboration with the Swedish group of Prof. A. Odfors, I collected a cohort of patients with muscle glycogenosis with polyglucosan bodies and identified the glycogenin-1 gene. Furthermore, I focused on muscle electron microscopy analysis to detect pathomechanisms causing muscle weakness in congenital myopathies. With this respect, I established a collaboration with Prof. Coren Ottenhjim at the VU University of Amsterdam for the study of contractility in single fiber muscle biopsies of patients with congenital myopathies. The results showed that reduced nebulin myopathies and ACTA1-related nemaline myopathies are associated with the brevity of fine filaments. In contrast, other nemaline myopathies do not exhibit these characteristics. We also studied another case of congenital myopathy that shows a high prevalence in the Netherlands due to a founder effect. These are the nemaline myopathies related to dominant mutation in KBTBD13 or NEM6. Muscle biopsies from this patient show no alteration in contractility but the alteration seems to reside in the binding with alpha actin. My future research work will be devoted to ameliorate the knowledges in muscle histopathology and to apply the technique of histopathology to discover and validate disease markers before and after new therapeutic approaches such as gene therapy, antisense oligonucleotides or small molecules. In particular, I will intensify my studies for the translational application to patients of new pharmacological therapies for ultra-congenital myopathies. On the clinical side, I broaden my field of interest to other muscular dystrophies such as Calpain 3 CAPN3 deficiency and FSHD1 muscular dystrophy. By participating in various grant applications, I also wish to contribute to the development of new treatments, thanks to the national and international collaborations I have developed over the last few years with several research groups specialized in the field of neuromuscular diseases.