Gene/syndrome under study
VPS35L (OMIM 618981); Ritscher-Schinzel syndrome (OMIM 619135)
Abstract
RSS is an ultra-rare condition characterized by multisystemic involvement (central nervous, cardiovascular, and musculoskeletal systems) with variable expressivity. Recent studies have identified biallelic VPS35L variants in four RSS patients, linking endosomal cargo recycling dysfunction—particularly affecting the Retriever complex (a key regulator of membrane protein trafficking via SNX17, CCC complex, and WASH complex)—to disease pathogenesis. Animal models have shown that VPS35L loss of function disrupts Retriever-SNX17 interaction, impairing developmental receptor recycling essential for skeletal and neuronal function.
We aim to gather information from as many affected individuals as possible to provide a more detailed phenotypic characterization of this condition and elucidate the pathogenic mechanisms underlying the disease performing in-vitro functional analysis.
Coordinating team
Dr. Ilaria Carelli – ilaria.carelli@unito.it
Dr. Federico Rondot MD – federico.rondot@unito.it
Prof. Alessandro Mussa MD PhD – alessandro.mussa@unito.it
Prof. Alfredo Brusco PhD – alfredo.brusco@unito.it
Institution
Città della Salute e della Scienza di Torino, Ospedale Regina Margerita, Torino
Neuroscience Department, University of Turin
Pediatric science Department, University of Turin
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: Yes
2- Resampling of patients: Yes
3- Linked to a translational/basic research project: Yes