Mendelian disorders of PI metabolizing enzymes

Biochim Biophys Acta. 2015 Jun;1851(6):867-81. doi: 10.1016/j.bbalip.2014.12.001. Epub 2014 Dec 12.

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.

Keywords: Genetic disease; Lowe syndrome; OCRL; PI kinase; PI phosphatase; Phosphoinositide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Diseases, Developmental / enzymology
  • Bone Diseases, Developmental / genetics*
  • Bone Diseases, Developmental / pathology
  • Disease Models, Animal
  • Gene Expression
  • Hereditary Sensory and Motor Neuropathy / enzymology
  • Hereditary Sensory and Motor Neuropathy / genetics*
  • Hereditary Sensory and Motor Neuropathy / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Limb Deformities, Congenital / enzymology
  • Limb Deformities, Congenital / genetics*
  • Limb Deformities, Congenital / pathology
  • Mice
  • Mutation*
  • Myopathies, Structural, Congenital / enzymology
  • Myopathies, Structural, Congenital / genetics*
  • Myopathies, Structural, Congenital / pathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositols / metabolism*
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • Phosphatidylinositols
  • Phosphatidylinositol 3-Kinases
  • Phosphoric Monoester Hydrolases