The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase.
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.
Attree
O
O
Department of Human Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104-6145.
Olivos
I M
IM
Okabe
I
I
Bailey
L C
LC
Nelson
D L
DL
Lewis
R A
RA
McInnes
R R
RR
Nussbaum
R L
RL
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
D011506:Proteins; D004247:DNA; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human; D000072181:Inositol Polyphosphate 5-Phosphatases