Ciliopathies

The term "ciliopathy" does not describe a strictly defined entity, but a pathogenetic concept - the dysfunction of primary (immobile) and mobile cilia. Because our work involves the identification of known (diagnostic) and as yet unknown (scientific) causes of a variety of genetic disorders, with special emphasis on retinal dystrophies, pediatric developmental disorder and malformation syndromes, ciliopathies inevitably represent a major focus at our Institute.

Primary cilia are sensory organelles of the cell surface and extracellular space that control cellular processes via the detection of extracellular signals. Formation, maintenance, disassembly, protein transport, and signaling pathways require the function of thousands of genes, nearly 700 of which are known to localize to or have ciliary functions in cilia.

Pathogenic variants in such "ciliary genes" can lead to a variety of heritable diseases. These "ciliopathies," consistent with the role of cilia in virtually all cell types, can affect virtually all organs and range from developmental defects with congenital malformations to late-manifesting dysfunction of individual organs; the retina and kidneys are particularly commonly affected.

Examples of diseases that can be considered ciliopathies in the strict sense are

• Joubert syndrome (JBTS)
• Meckel-Gruber syndrome (MKS)
• Bardet-Biedl syndrome (BBS)
• Jeune asphyxiating thoracic dystrophy (JATD)
• Oro-facio-digital syndrome (OFD)
• Leber's congenital amaurosis (LCA), retinal dystrophies (some subtypes)
• Usher syndrome (USH)
• Senior-Løken syndrome (SLSN)
• Heterotaxies
• Polydactyly
• Nephronophthisis (NPHP)
• Polycystic kidney disease (PKD)
• Primary Ciliary Dyskinesia (PCD)

Collaborations: We work closely with various patient organizations and specialized university centers.

Diagnostics: We use the most modern methods of high-throughput sequencing and genomic structural analysis to uncover even complicated causes of ciliopathies.

Research: By identifying new genes for Joubert syndrome (PMIDs: 21633164, 26386247, 25044745) and retinal ciliopathies, among others, we continuously contribute to a better understanding of this group of diseases.

Publications:

• Identification of CEP162 mutations as a cause of late-manifest retinal ciliopathy; PMID: 36862503
• Identification of the KIF7 gene for Joubert syndrome type 12 (JBTS12); PMID: 21633164
• Identification of the KIAA0586 gene for Joubert syndrome type 23 (JBTS23); PMID: 26386247
• Identification of POC1B mutations as a cause of severe retinal ciliopathy; PMID: 25044745
• Identification of the retinal modifier and digenic Usher syndrome gene PDZD7; PMID: 20440071
• Identification of the gene for Usher syndrome type 1D (USH1D); PMID: 11138009
• Identification of the gene for Usher syndrome type 2D (USH2D); PMID: 17171570