Nature 358, 239 - 242 (16 July 1992); doi:10.1038/358239a0

The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase

Olivier Attree^*†, Isabelle M. Olivos^*, Ichiro Okabe^†‡, L. Charles Bailey^*, David L. Nelson^§, Richard A. Lewis^§, Roderick R. Mclnnes^¶ & Robert L. Nussbaum^*‡£

^* Department of Human Genetics, and ^‡ Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104-6145, USA^§ Institute for Molecular Genetics and Department of Ophthalmology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA ^¶ Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada ^† Present addresses; CRSSA, Unite de Biologie Moleculaire. 38702 La Tranche Cedex, Grenoble, France (O.A.); and Department of Pediatrics, Jichi Medical School, Minamikawachi-Machi, Kawachi-Gun, Tochigi-Ken, Japan 329-04 (I.O.).^£ To whom correspondence should be addressed.

LOWE'S oculocerebrorenal syndrome^1–3 (OCRL) is a human X-linked developmental disorder of unknown pathogenesis^4–8 and has a pleiotropic phenotype affecting the lens, brain and kidneys. The OCRL locus has been mapped to Xq25-q26 by linkage^9–11 and by finding de novoX; autosome translocations at Xq25-q26 in two unrelated females with OCRL^12,13. 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.

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