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Mutations in INPP5K, encoding a phosphoinositide 5-phosphatase, cause congenital muscular dystrophy with cataracts and mild cognitive impairment.
Am. J. Hum. Genet. 100, 523-536 (2017)
Phosphoinositides are small phospholipids that control diverse cellular downstream signaling events. Their spatial and temporal availability is tightly regulated by a set of specific lipid kinases and phosphatases. Congenital muscular dystrophies are hereditary disorders characterized by hypotonia and weakness from birth with variable eye and central nervous system involvement. In individuals exhibiting congenital muscular dystrophy, early-onset cataracts, and mild intellectual disability but normal cranial magnetic resonance imaging, we identified bi-allelic mutations in INPP5K, encoding inositol polyphosphate-5-phosphatase K. Mutations impaired phosphatase activity toward the phosphoinositide phosphatidylinositol (4,5)-bisphosphate or altered the subcellular localization of INPP5K. Downregulation of INPP5K orthologs in zebrafish embryos disrupted muscle fiber morphology and resulted in abnormal eye development. These data link congenital muscular dystrophies to defective phosphoinositide 5-phosphatase activity that is becoming increasingly recognized for its role in mediating pivotal cellular mechanisms contributing to disease.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cognitive Impairment ; Congenital Muscular Dystrophy ; Early Cataracts ; Inpp5k ; Phosphoinositide Phosphatase; Marinesco-sjogren-syndrome; Polyphosphate Phosphatase Skip; Unfolded Protein Response; Endoplasmic-reticulum; Membrane Trafficking; Signal-transduction; Skeletal-muscle; Myopathy; Gene; Disease
ISSN (print) / ISBN 0002-9297
e-ISSN 1537-6605
Zeitschrift American Journal of Human Genetics, The
Quellenangaben Band: 100, Heft: 3, Seiten: 523-536 Artikelnummer: , Supplement: ,
Verlag Elsevier ; Cell Press
Verlagsort New York, NY
Begutachtungsstatus peer-reviewed