THE LOWE OCULOCEREBRORENAL SYNDROME GENE ENCODES A PROTEIN HIGHLY HOMOLOGOUS TO INOSITOL POLYPHOSPHATE-5-PHOSPHATASE

LOWE'S oculocerebrorenal syndrome1-3 (OCRL) is a human X-linked developmental disorder of unknown pathogenesis4-8 and has a pleiotropic phenotype affecting the lens, brain and kidneys. The OCRL locus has been mapped to Xq25-q26 by linkage9-11 and by finding de novo X; autosome translocations at Xq25-q26 in two unrelated females with OCRL12,13 . 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.