title: Mendelian disorders of PI metabolizing enzymes.
abstract: More than twenty different genetic diseases have been described that are caused by mutations in phosphoinositide metabolizing enzymes, mostly in phosphoinositide phosphatases. Although generally ubiquitously expressed, mutations in these enzymes, which are mainly loss-of-function, result in tissue-restricted clinical manifestations through mechanisms that are not completely understood. Here we analyze selected disorders of phosphoinositide metabolism grouped according to the principle tissue affected: the nervous system, muscle, kidney, the osteoskeletal system, the eye, and the immune system. We will highlight what has been learnt so far from the study of these disorders about not only the cellular and molecular pathways that are involved or are governed by phosphoinositides, but also the many gaps that remain to be filled to gain a full understanding of the pathophysiological mechanisms underlying the clinical manifestations of this steadily growing class of diseases, most of which still remain orphan in terms of treatment. This article is part of a Special Issue entitled Phosphoinositides.
authors.affiliation: Telethon Institute of Genetics and Medicine, Pozzuoli (NA), Italy.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Staiano
authors.affiliation: Telethon Institute of Genetics and Medicine, Pozzuoli (NA), Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: De Leo
authors.affiliation: Telethon Institute of Genetics and Medicine, Pozzuoli (NA), Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Persico
authors.affiliation: Telethon Institute of Genetics and Medicine, Pozzuoli (NA), Italy. Electronic address: dematteis@tigem.it.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: De Matteis
mesh_terms: D000818:Animals; D001848:Bone Diseases, Developmental / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D015417:Hereditary Sensory and Motor Neuropathy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D017880:Limb Deformities, Congenital / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010716:Phosphatidylinositols; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases
keywords: Genetic disease; Lowe syndrome; OCRL; PI kinase; PI phosphatase; Phosphoinositide