Identification and characterization of pathogenic mutations in GPI-anchor deficiencies

• Applicant: Professor Dr. Uwe Kornak, since 6/2018
• Subject Area: Human Genetics
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 290617713

GPI-anchor deficiencies are a new class of genetic disorders that are caused by germline, as well as somatic mutations in genes of the GPI-anchor synthesis. Patients with congenital GPI-anchor deficiencies have a syndromic form of intellectual disability and neurologic features such as epilepsies are of utmost clinical interest. In paroxysmal nocturnal hemoglobinuria cells of the myeloid system acquire somatic mutations and become attackable by the complement system.The pathogenic mutations that we found helped to deepen our understanding of the biochemical and biological mechanisms of the GPI-anchor synthesis pathway. In this project we intend to sequence patients with GPI-anchor deficiencies with unknown cause and we aim to identify further disease related genes with complex bioinformatics filtering methods. To increase our understanding of genotype phenotype correlations we plan to analyze specific pathogenic mutations in vitro and in vivo.Aim 1: Expansion of a cohort of patients with GPI-anchor deficiency of unknown causeAim 2: Bioinformatics analysis of whole genome sequences selected cases.Aim 3: Functional analysis of specific pathogenic mutations in mice with CRISPR/Cas9

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Peter Krawitz, until 6/2018