Our research will contribute to a better understanding of the pathomechanism of PACS2 Syndrome most likely related to the alterations in mitochondria-endoplasmic reticulum interaction, mitochondrial dysfunction and lipid metabolism alterations.
The project will be implemented in cooperation of two teams led by Prof. Mariusz Wieckowski and Prof. Agnieszka Dobrzyn from the Nencki Institute. On the social side, the project is supported by the PACS2 Research Foundation, which unites PACS2 patients and their families.
First publication on PACS2 mutation comes from 2018. Since then, ca. 20 cases were covered in publications and around 40-50 people (mainly children) around the globe have heard diagnosis connected with this mutation. Nevertheless, it is hard to diagnose PACS2 syndrome as the phenotype is not strictly specific and currently the most common way to learn about the mutation is to perform whole exome sequencing.
This is quite exceptional, single variant mutation - in most of the cases it occurs in the same place c.625G>A (p.Glu209Lys) (in just few ones: c.631G>A (p.Glu211Lys)) leading to change of one protein - coding lysine instead of glutamate. At the same time, it is heterozygous variant what means that mutation impacts only one allele while the other one works correctly. Unfortunately, its pattern is autosomal dominant meaning that mutation in just one allele is leading to disease. Almost all the cases are de novo - it is not inherited from parents. Except for one case featured just in February 2022 (LINK). At least it is what we know for now. Basic research, conducted in parallel with clinical trials, are crucial for the development of targeted therapy in PACS2. They will allow to investigate the effectiveness of the used therapy as well as to implement new therapeutic solutions for PACS2 patients.