Yunis-Varon syndrome(English)

  • (OMIM #216340) an autosomal recessive disorder with poor outcome, comprising skeletal anomalies (cleidocranial dysplasia; absence/hypoplasia of thumbs, halluces and distal phalanges; gracile bones; hypomineralization and fractures), dysmorphism, global developmental delay and intracytoplasmic vacuolation in brain and other tissues. All hitherto-reported pathogenic variants affect FIG4, a lipid phosphatase involved in phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] metabolism. FIG4 interacts with PIKfyve, a lipid kinase, via the adapter protein VAC14; all subunits of the resulting complex are essential for PtdIns(3,5)P2 synthesis in the endolysosomal membrane compartment. Altered endolysosomal trafficking is evidenced by the presence of multiple, enlarged vacuoles expressing endolysosomal markers including LAMP
  • FIG4, VAC14, LAMP
  • Congenital disorders, Musculoskeletal system, Brain (dys)function
  • https://doi.org…38/ejhg.2017.99