Inherited myopathies and congenital myasthenic syndromes in a cohort from different regions of Turkey

Myopathies include a clinically, genetically, and mechanistically heterogeneous group of diseases characterized by muscle weakness and fatigue. Congenital myasthenic syndromes (CMS) are characterized by symptoms such as easy fatigue, muscle weakness, and ptosis. Definitive diagnosis of the disease is often difficult, but next-generation sequencing technologies, especially whole exome sequencing (WES), have contributed to their diagnostic process. This thesis involves the use of WES, bioinformatic analysis, and wet-lab to understand the genetic basis of Turkish Myopathy and CMS patients. In total, 23 cases were solved, including eight novel variants, in 30 index patients. The number of unsolved cases was seven, including three sporadic cases. With this thesis, in the cohort under study, the genetic causes of myopathies and congenital myasthenia syndrome have been revealed and differential diagnoses guided. WES is the current gold standard for genetic investigation of inherited disorders, but it has also limitations and challenges. The diagnosis rate is positively correlated with gene-disease associations, and it is suggested that the more associations, the higher the diagnostic yield. The discovery of new causal genes through large cohort studies is also important for this reason. This thesis is expected to contribute to a better understanding of the clinical and genetic picture of myopathy and CMS patients in Turkey, and thus to a better comprehension of the complicated phenotype-genotype correlations of muscle disorders. Such studies will help to shape a hopeful future in the genetic era.