title: The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase.
abstract: Lowe's oculocerebrorenal syndrome (OCRL) is a human X-linked developmental disorder of unknown pathogenesis and has a pleiotropic phenotype affecting the lens, brain and kidneys. The OCRL locus has been mapped to Xq25-q26 by linkage and by finding de novo X; autosome translocations at Xq25-q26 in two unrelated females with OCRL. Here we use yeast artificial chromosomes with inserts that span the X chromosomal breakpoint from a female OCRL patient in order to isolate complementary DNAs for a gene that is interrupted by the translocation. We show that the transcript is absent in both female OCRL patients with X; autosome translocations and that it is absent or abnormally sized in 9 of 13 unrelated male OCRL patients with no detectable genomic rearrangement. The open reading frame encodes a new protein with 71% similarity to human inositol polyphosphate-5-phosphatase. Our results suggest that OCRL may be an inborn error of inositol phosphate metabolism.
authors.affiliation: Department of Human Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104-6145.
authors.forename: O
authors.initials: O
authors.lastname: Attree
authors.forename: I M
authors.initials: IM
authors.lastname: Olivos
authors.forename: I
authors.initials: I
authors.lastname: Okabe
authors.forename: L C
authors.initials: LC
authors.lastname: Bailey
authors.forename: D L
authors.initials: DL
authors.lastname: Nelson
authors.forename: R A
authors.initials: RA
authors.lastname: Lewis
authors.forename: R R
authors.initials: RR
authors.lastname: McInnes
authors.forename: R L
authors.initials: RL
authors.lastname: Nussbaum
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D015723:Gene Library; D008040:Genetic Linkage; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D008297:Male; D008969:Molecular Sequence Data; D009800:Oculocerebrorenal Syndrome / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic; D014960:X Chromosome
chemical_list: D011506:Proteins; D004247:DNA; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human; D000072181:Inositol Polyphosphate 5-Phosphatases