Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel

Mucolipidosis type IV (MLIV) is a developmental neurodegenerative disorder characterized by severe neurologic and ophthalmologic abnormalities, The ML IV gene, ML4 (MCOLN1), has recently been localized to chromosome 19p13.2-13 .3 by genetic linkage. Here we report the cloning of a novel transient rece ptor potential cation channel gene and show that this gene is mutated in pa tients with the disorder, ML4 encodes a protein, which we propose to call m ucolipin, which has six predicted transmembrane domains and is a member of the polycystin II subfamily of the Drosophila transient receptor potential gene family. The role of a potential receptor-stimulated cation channel def ect in the pathogenesis of mucolipidosis IV is discussed.