Oculocerebrorenal syndrome of Lowe (OCRL, OMIM 309000), also known as
Lowe syndrome, is a rare X-linked multisystem disorder characterized by congenital
cataracts,
mental retardation, and
Fanconi syndrome of the kidney proximal tubules.
Lowe syndrome is caused by mutations in the gene encoding a member of the
inositol polyphosphate-5-phosphatase
protein family (OCRL1) on chromosome Xq26.1. OCRL1 contains 24 exons and encodes a 105-kDa
phosphatidylinositol (4,5) bisphosphate 5-phosphatase. An OCRL1
isoform generated by alternative splicing is predominantly expressed in brain, and localizes to the trans-Golgi network, lysosomes, and endosomes. Impaired
inositol polyphosphate-5-phosphatase activity elevates
phosphatidylinositol (4,5) bisphosphate levels that are required for vesicle trafficking within the Golgi apparatus, actin cytoskeleton remodeling closely associated with Golgi, and endosomal membrane trafficking. Accordingly, abnormalities in the actin cytoskeleton may influence the function of renal epithelial cells in patients with
Lowe syndrome. OCRL1 mutations exist in about 95% of patients with
Lowe syndrome, and new mutations occur in 32% affected males. We here describe a Japanese male with the mild phenotype of
Lowe syndrome. Physical examination revealed mild congenital bilateral
cataracts, mild mental disability, and short stature.
Proteinuria was also mild with a high β2-microglobulinuria level. Nucleotide sequence analysis identified a hemizygous mutation (T-to-C transition) at
nucleotide 2039 in exon 18 that substitutes Ser (TCT) for Phe (TTT) at
amino acid position 680. This missense mutation is located outside the known catalytic domain that is encoded by exons 4 through 15. The present patient carries a novel OCRL1 mutation that is helpful for genetic counseling.