title: Identification of two novel mutations in the OCRL1 gene in Japanese families with Lowe syndrome.
abstract: The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked disorder with features of congenital cataracts, Fanconi syndrome of the renal tubule, and mental retardation. The OCRL1 gene has been positionally cloned and shown to encode a phosphatidylinositol 4,5-biphosphate-5-phosphatase. OCRL is thus thought to be an inborn error of inositol polyphosphate metabolism. We analyzed the gene in two Japanese OCRL patients and their families by DNA sequencing and mismatch polymerase chain reaction (PCR) followed by restriction digestion. A novel nonsense mutation (C1399T) replacing the glutamine of codon 391 (Gln 391 Stop) was identified in exon 12 in 1 patient and also in his mother. A novel missense mutation (C1743G) was identified in exon 15 in the second patient. his mother and maternal grandmother. The missense mutation predicts a substitution of serine for arginine (Ser 505 Arg) in a domain highly conserved among the inositol-5-phosphatase family. Our observations expand the range of OCRL1 mutations that cause Lowe syndrome, and will be useful for genetic counseling in these two families.
authors.affiliation: Department of Hygiene and Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.forename: A
authors.initials: A
authors.lastname: Sakurai
authors.forename: K
authors.initials: K
authors.lastname: Arakawa
authors.forename: M
authors.initials: M
authors.lastname: Shimazu
authors.forename: K
authors.initials: K
authors.lastname: Wakui
authors.forename: K
authors.initials: K
authors.lastname: Furihata
authors.forename: Y
authors.initials: Y
authors.lastname: Fukushima
mesh_terms: D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009800:Oculocerebrorenal Syndrome / Q000235:genetics*; D010375:Pedigree; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D011506:Proteins; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human