Cognitive and behavioral profile of the oculocerebrorenal syndrome of Lowe

Kenworthy, Lauren; Park, Taesung; Charnas, Lawrence

doi:10.1002/ajmg.1320460312

Cited by 51 publications

(42 citation statements)

References 29 publications

(16 reference statements)

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“…Descriptions of additional infants with similar features led to the identification of the cardinal features of the syndrome: congenital cataracts, Fanconi syndrome of the proximal renal tubules, and mental retardation inherited as an X-linked trait (2). OCRL is a rare disease with only a few hundred known patients in the United States (3).…”

Section: Introductionmentioning

confidence: 99%

“…Mean IQ is in the moderate range (40 Ͻ IQ Ͻ 54) although 25% of patients score above and 25% below this interval (3,6). Neonatal and infantile hypotonia of central nervous system origin is also a frequent feature but improves or disappears with age (2).…”

Section: Introductionmentioning

confidence: 99%

“…Neonatal and infantile hypotonia of central nervous system origin is also a frequent feature but improves or disappears with age (2). Neuropathological examination of OCRL brains has been reported to range from completely normal to variously abnormal, with no specific pathologic findings (2,3,7).…”

Section: Introductionmentioning

confidence: 99%

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Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice.

et al. 1998

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The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked human genetic disorder characterized by mental retardation, congenital cataracts, and renal tubular dysfunction. The Lowe syndrome gene, OCRL1 , encodes a phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi complex. The pathogenesis of Lowe syndrome due to deficiency of a phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi complex is unknown. We have used targeted disruption in embryonic stem cells to make mice deficient in Ocrl1 , the mouse homologue for OCRL1 , as an animal model for the disease. Surprisingly, mice deficient in Ocrl1 do not develop the congenital cataracts, renal Fanconi syndrome, or neurological abnormalities seen in the human disorder. We hypothesized that Ocrl1 deficiency is complemented in mice by inositol polyphosphate 5-phosphatase ( Inpp5b ), an autosomal gene that encodes a phosphatidylinositol bisphosphate 5-phosphatase highly homologous to Ocrl1. We created mice deficient in Inpp5b ; the mice were viable and fertile without phenotype except for testicular degeneration in males beginning after sexual maturation. We crossed mice deficient in Ocrl1 to mice deficient in Inpp5b. No liveborn mice or embryos lacking both enzymes were found, demonstrating that Ocrl1 and Inpp5b have overlapping functions in mice and suggesting that the lack of phenotype in Ocrl1 -deficient mice may be due to compensating Inpp5b function. (

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice.

et al. 1998

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“…A recent study showed that OCRL1 mutations lead to a Dentlike phenotype, Dent-2 disease, which manifests mild developmental delays and visually insignificant peripheral cataracts (Hoopes et al 2005: Bökenkamp et al 2009). Kenworthy et al (1993) reported that 47 males with Lowe syndrome had a mean IQ of 45-54, characteristic of moderate mental impairment, and that the IQs of 25% were within the normal range (>70). Further, >80% exhibited maladaptive behavior, particularly stubbornness, temper tantrums, and other stereotypic behaviors.…”

Section: Discussionmentioning

confidence: 99%

“…Most patients show behavioral disturbances, irritability, outbursts of anger, and stereotypic behavior (Kenworthy et al 1993). Therefore, the severity of the developmental disorder may remain mild in patients with the missense mutations.…”

Section: Discussionmentioning

confidence: 99%

A Novel <i>OCRL1</i> Mutation in a Patient with the Mild Phenotype of Lowe Syndrome

Sugimoto

Nishi

Miyazawa

et al. 2014

Tohoku J. Exp. Med.

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Hypothesis III

Palumbo

Maughan²,

Kurlan³

1997

Arch Neurol

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Tourette syndrome (TS) is a hereditary condition characterized by the presence of chronic, multiple motor tics and is commonly associated with obessive-compulsive behavior, attentional and executive dysfunction, and aggressive behavior. A wide range of other genetic and environmental conditions that interfere with normal basal ganglia developmental processes can produce a clinical syndrome that we call the developmental basal ganglia syndrome (DBGS), and which closely resembles TS. Failure to distinguish TS from other causes of DBGS has probably hampered research efforts aimed at clarifying the neurobiological mechanisms, localizing the genetic defect, assessing therapy, and establishing accurate prevalence rates for TS.

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Cognitive and behavioral profile of the oculocerebrorenal syndrome of Lowe

Abstract: The diagnosis of OCRL is compatible with normal intelligence. Maladaptive behaviors significantly interfere with adaptive functions. These behaviors appear to define a characteristic behavioral phenotype in OCRL.

Cited by 51 publications

References 29 publications

Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice.

Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice.

A Novel <i>OCRL1</i> Mutation in a Patient with the Mild Phenotype of Lowe Syndrome

Hypothesis III

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