Frauke Hinrichs, Hauke Baumann, Katja Lohmann, Sophie Isay, Eva Hebert, Sofia Steinrücke, Lara Lange

Genetics of Rare Diseases

Katja Lohmann, PhD

Team: Katja Lohmann (section leader); Eva Hebert (PhD student); Hauke Baumann (PhD student); Frauke Hinrichs (technician); Sofia Steinrücke (MD student); Lara Lange (MD student); Julia Seelinger (HiWi); Sophie Isay (HiWi)

The research team “Genetic causes of movement disorders” focuses on the identification and evaluation of mutations and genetic risk factors in different movement disorders with a main focus on dystonia but also on Parkinson disease, restless legs syndrome, and spinocerebellar ataxias. We recently identified the mutation leading to DYT4 dystonia in an Australian family using genome-wide linkage analysis and next generation sequencing techniques. These approaches are currently used to reveal the underlying genetic causes in several other families as well as sporadic patients.

We also elucidated the first genetic risk factors for musician´s dystonia by carrying out a genome-wide association study. Musician’s dystonia is an important medical problem in musicians that is known to affect 1-2% of professional instrumentalists. As a type of focal task-specific dystonia, it presents with painless muscular incoordination or loss of voluntary motor control when a musician is playing his instrument.

Another project involves the characterization of the DYT6 dystonia-causing gene THAP1 and its encoded protein. For instance, we revealed that THAP1 functions as a transcription factor that regulates the expression of the DYT1 dystonia-causing gene TorsinA as well as its own expression. We identified several disease-causing mutations and performed functional studies of the mutants.

Projects are funded by the German Research Foundation (DFG), the Bachmann Strauss Dystonia & Parkinson’s Disease Foundation, the Renate-Maaß Foundation, and intramural grant support.

We collaborate with several national and international colleagues including Prof. Eckart Altenmüller (Hanover University of Music, Drama and Media, Hanover, Germany), Prof. Laurie Ozelius (Mount Sinai School of Medicine, New York, NY), and Prof. Joris Veltman (University Medical Centre St Radboud, Nijmegen, The Netherlands).

Figure: Manhattan plot of the genome-wide association study in musician´s dystonia. The results of the first stage of the association study are shown. The log10P-values are plotted against chromosomal positions using 558,245 genotyped SNPs.