Deciphering the molecular pathophysiology of muscular dystrophies facilitated by disease gene discovery using integrative next generation sequencing

• Applicant: Professor Dr. Sebahattin Cirak
• Subject Area: Human Genetics ; Pediatric and Adolescent Medicine
• Term: from 2014 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 251076596

Muscular dystrophies are a diverse group of inherited disorders that lead to progressive muscle wasting and disability. Many forms are lethal. These inborn disorders are due to misspellings and errors (mutations) in the genetic code (genes) containing the information for the generation and proper function of muscles. In recent years, a number of disease-causing gene mutations have been uncovered but unfortunately in about 50% of the patients the underlying disease genes are unknown. Currently, there is no curative treatment for muscular dystrophy available for most of the muscular dystrophies. There is a disease-ameliorating therapy in clinical development for the common form Duchenne Muscular Dystrophy (Cirak et. al., 2011). Unfortunately, for other forms, the underlying disease genes and mechanisms are unknown. The lack of knowledge of disease-causing genes leads to absence of understanding of underlying disease mechanisms and hampers ultimately the development of specific therapies. In this proposal, we aim to use the latest genetic technologies to find the disease-causing mutations in unsolved families/cases with muscular dystrophy. This will enable us to provide genetic diagnosis and counseling for the patients and families. Finally, we want to investigate and understand the biochemical function of the disease genes and the disease pathophysiology in murine models. The obtained scientific knowledge will enable the development of novel targeted molecular therapies for muscular dystrophies.

• DFG Programme: Independent Junior Research Groups