title: Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families.
abstract: Autosomal dominant cone dystrophy (CORD5) (MIM 600977) is a rare disease predominantly affecting cone photoreceptors. Here we refine the CORD5 locus previously mapped to 17p13 from 27 to 14.3 cM and identified a missense mutation, Q626H in the phosphatidylinositol transfer (PIT) membrane-associated protein (PITPNM3) (MIM 608921) in two Swedish families. PITPNM3, known as a human homologue of the Drosophila retinal degeneration B (rdgB), lacks the N-terminal PIT domain needed for transport of phospholipids, renewal of photoreceptors membrane and providing the electroretinogram (ERG) response to light. In our study, the mutation causing CORD5 is located in the C-terminal region interacting with a member of nonreceptor protein tyrosine kinases, PYK2. Our finding on the first mutation in the human homologue of Drosophila rdgB indicates novel pathways and a potential important role of the PITPNM3 in mammalian phototransduction.
authors: Medical and Clinical Genetics, Department of Medical Biosciences, Umeå University, SE 901 85 Umeå, Sweden.
authors: Linda
authors: L
authors: Köhn
authors: Konstantin
authors: K
authors: Kadzhaev
authors: Marie S I
authors: MS
authors: Burstedt
authors: Susann
authors: S
authors: Haraldsson
authors: Bengt
authors: B
authors: Hallberg
authors: Ola
authors: O
authors: Sandgren
authors: Irina
authors: I
authors: Golovleva
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics*; D005260:Female; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012162:Retinal Degeneration / Q000235:genetics*; D017948:Retinal Rod Photoreceptor Cells; D016415:Sequence Alignment; D013548:Sweden
chemical_list: D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; C117885:PITPNM3 protein, human; D051418:Focal Adhesion Kinase 2