1/9. prenatal diagnosis of Lowe syndrome by OCRL1 messenger rna analysis.Prenatal screening of oculo-cerebro-renal syndrome of Lowe (OCRL; McKusick 309000) was performed using cultured amniocytes. Following identification of defective mRNA expression in the OCRL; gene of the proband's fibroblasts, the mRNA size and quantity of the cultured amniocytes were compared. Based on this analysis, the fetus was diagnosed as being normal and was subsequently delivered as a healthy boy. This is the first reported successful prenatal screening of OCRL using a comparison with defective mRNA of OCRL1 from affected subjects.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
2/9. Unusual renal features of Lowe syndrome in a mildly affected boy.The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by congenital cataracts, mental retardation, and renal tubular dysfunction. The gene responsible for OCRL was identified by positional cloning and encodes a lipid phosphatase, phosphatidylinositol 4,5, bisphosphate [PtdIns(4,5)P2]5-phosphatase, which localizes to the golgi apparatus and is suspected to play a role in Golgi vesicular transport [Suchy et al., 1995]. In addition to the ocular and renal manifestations, most boys with OCRL have cognitive problems and maladaptive behaviors including tantrums and stereotypies. We report a boy with a history of congenital cataracts and mild developmental delay who was also found to have hematuria with proteinuria but minimal signs of renal tubular dysfunction. Subsequent renal biopsy was compatible with a diagnosis of a noncomplement fixating chronic glomerulonephritis. Despite the atypical renal findings, skin fibroblast analysis for PtdIns (4,5)P2 5-phosphatase was performed, and enzyme activity was low, consistent with the diagnosis of OCRL. Western blot analysis from cell lysates showed the ocrl protein was decreased in size and amount. Our report shows atypical renal features of OCRL in a mildly affected boy. The possibility of OCRL should be considered in boys with cataracts and glomerular disease, even in the absence of renal tubular defects and frank mental retardation usually associated with the syndrome. Am. J. Med. Genet. 95:461-466, 2000. Published Wiley-Liss, Inc.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
3/9. Renal disease in Arima syndrome is nephronophthisis as in other Joubert-related Cerebello-oculo-renal syndromes.Clinicopathological features of the renal disease in Arima syndrome were studied in five autopsy cases. All cases showed insidious development of end-stage renal disease during childhood, preceded by polyuria/polydipsia, anemia, and growth failure. Decreased urinary concentrating ability and excessive sodium loss were the characteristic laboratory findings. Gross examination showed that both kidneys were small and showed multiple cysts of various sizes. The histological examinations revealed chronic sclerosing tubulo-interstitial nephropathy with cystic tubuli predominantly located at cortico-medullary areas. These observations suggest that the renal disease in Arima syndrome is in accordance with nephronophthisis both clinically and pathologically. Contrary to the previous literature which described that Arima syndrome can be distinguished from other Joubert-related cerebello-oculo-renal syndromes by its unique renal disease, i.e., cystic dysplastic kidney (CDK), our study indicates that the phenotype of the renal disease is common among these syndromes as well as abnormalities in other organs, suggesting the underlying similar molecular mechanisms.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
4/9. cataract in a fetus at risk for oculo-cerebro-renal syndrome (Lowe).A high-risk pregnancy for X-linked recessive inherited Lowe's syndrome was terminated due to a male karyotype in the cultured amniotic fluid cells. The eyes of the male fetus showed specific cataracteous changes of the lens. A posterior lenticonus was due to a defect of the lens capsule. The lenses were of normal size. Loss of lens material through a lens capsule defect could account for the small discoid lens usually seen in Lowe's syndrome. amino acids in amniotic fluid had normal concentrations except lysine and proline which were markedly elevated.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
5/9. Urinary acid glycosaminoglycans in a patient with oculo-cerebro-renal syndrome.An 18-year-old boy with oculo-cerebro-renal syndrome excreted a large amount of acid glycosaminoglycans in urine. The identification and characterization of the acid glycosaminoglycans were carried out by the methods of preparative column electrophoresis, ion exchange chromatography, gelfiltration, paper chromatography of the chondroitinase digests and chemical analysis. On admission to hospital, the main components of the urinary acid glycosaminoglycans were undersulfated chondroitin 4-sulfate of large molecular weight and heparan sulfate. Three months after oral administration of the supplement of alkali, the excretion of heparan sulfate and the molecular size of chondroitin 4-sulfate decreased significantly, although the amount of urinary acid glycosaminoglycans remained at a high level (about 25 mg/day). The decrease of heparan sulfate and the shift to a smaller molecule of chondroitin 4-sulfate were coincident with the improvement in clinical and laboratory findings. These results suggest that the abnormal metabolism of acid glycosaminoglycans is a characteristic manifestation in this case and the studies on ground substance metabolism might be an important approach to the pathogenesis of this syndrome.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
6/9. Clinicopathological studies of oculo cerebrorenal syndrome of Lowe, Terrey and MacLachlan.A thirty-three-year-old male with Lowe's syndrome had cataract; nystagmus, buphthalmos, prominent frontal bossing, growth and mental retardation, aminoaciduria, proteinuria, rickets, areflexia, genu valgum, piercing cry and head-banging being among the presenting features. The rickety changes improved over a period of years with the administration of vitamin D2. Pathological changes include: (1) tubular damage in the kidneys and hypertrophies of Bowman's capsules; (2) small brain with ventricular dilatation with thickened meninges, small corpus callosum, small size of pyramidal tracts and medial leminisci, neurofibrillary tangles in the pyramidal cells of the Ammon's horn and frontal lobe; (3) eye changes of buphthalmos, congenital cataracts and thickening of Descemet's membrane; (4) testicular atrophy--both testes showing peritubular fibrosis with an increase of fibrous tissue in the interstitial tissue. azoospermia was present linked with poor development of spermatogonia and spermatocytes. The lumina of the seminiferous tubules were filled with foamy exudate.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
7/9. Clinicopathologic and molecular-pathologic approaches to Lowe's syndrome.The oculocerebrorenal syndrome of Lowe (OCRL), an X-linked disorder involving several organ systems, including the eyes, nervous system, and kidneys, is often difficult to diagnose because few pathologic data of diagnostic features about OCRL are available, and its rarity has hampered comprehensive investigations into its clinical spectrum. Recently, the genetic and biochemical abnormalities responsible for this syndrome have been reported. We have synthesized a cDNA probe of the OCRL locus using a polymerase chain reaction, in which there is no homology of cDNA sequence with human inositol polyphosphate-5-phosphatase (HUMINP5P); we have taken a genetic approach to diagnose this disorder in a 10-year-old male by using Northern blotting and have demonstrated the expression of mRNA in human tissues of a 17-week fetus by in situ hybridization. This paper presents a new method that should be an easy and helpful tool for diagnosing OCRL and that contributes a new aspect of this syndrome through in situ hybridization histochemical staining of normal fetal tissues.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
8/9. Acinic cell carcinoma of the parotid in children.The imaging findings of two children with acinic cell carcinoma of the parotid gland are presented. Ultrasonic features are emphasized. One of these children, a 6-year-old boy, suffers from the oculocerebrorenal syndrome of Lowe, a rare congenital, inherited condition manifested by defects of the nervous system (mental retardation, hypotonia), eyes (cataracts, glaucoma) and kidneys. To date, no known association exists between these two rare entities. The other child, a 10-year-old girl, was otherwise well. The ultrasound findings of both cases demonstrate features more classic for a benign intraparotid mass than for a potentially malignant lesion. The possibility of acinic cell carcinoma should be considered if a well-defined, relatively homogenously hypo-echoic intraparotid mass is encountered in a child, especially if cystic spaces are present.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
9/9. oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene derived from three patients with different phenotypes.The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked multisystem disorder with major abnormalities of eyes, nervous system, and kidneys. Clinical manifestations include congenital cataract, mental retardation, and renal tubular dysfunction. A gene (OCRL1) responsible for OCRL was identified by positional cloning and its product OCRL-1 protein was shown to be a phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] 5-phosphatase localized to the golgi apparatus. We describe three mutations in OCRL1, one in a patient with severe phenotype and two in patients with moderate phenotype (degree of mental retardation and musculoskeletal abnormalities). The patient with severe phenotype had a G-to-A transition at nucleotide (nt) 1,739, causing an Arg-to-Gln substitution at amino acid 577, and one patient with moderate phenotype had a C-to-G transversion at nt 1,812, leading to a His-to-Gln substitution at amino acid 601. Both Arg-577 and His-601 are encoded by exon 15 and are probably important for proper function of this protein, since these are conserved in various enzymes catalyzing dephosphorylation of inositol compounds. In the other patient with the moderate phenotype, there was a G-to-A transition at nt 2,797 located at the 3'-end of exon 22. This substitution led to a skip of the same exon as well as conversion of codon-930 from GCT (Ala) to ACT (Thr) in the normal-size transcript. When we measured the enzyme activity in skin fibroblasts from the three patients, the activity was less than 10%, compared to findings in normal controls. Western blot analysis showed absence or severe decrease in OCRL-1 protein in cell lysates derived from these patients.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |