Lowe Oculocerebrorenal Syndrome

Objective/Background. To describe an uncommon, life-threatening condition such as angiosarcoma of a fistula for hemodialysis occurring in a transplant recipient affected by Lowe’s syndrome. Summary. We present the case of a 56-year-old male kidney transplant recipient affected by Lowe’s syndrome, also known as oculocerebrorenal syndrome, a rare X-linked disorder characterized by congenital cataracts, hypotonia, intellectual disability, and Fanconi-like renal tubular dysfunction, who was diagnosed with angiosarcoma of a functioning arteriovenous fistula for hemodialysis. Conclusion. Angiosarcoma is a rare soft tissue tumor, and only 22 cases of angiosarcoma of arteriovenous fistulae were described so far; although a correlation between Lowe’s syndrome and a higher risk of tumor compared to the general population has not been described so far, the mechanisms of disease causation could be an interesting starting point for future studies on a possible connection between the two events.

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Evidence for a discrete behavioral phenotype in the oculocerebrorenal syndrome of lowe

American Journal of Medical Genetics ◽

10.1002/ajmg.1320590304 ◽

1995 ◽

Vol 59 (3) ◽

pp. 283-290 ◽

Cited By ~ 27

Author(s):

Lauren Kenworthy ◽

Lawrence Charnas

Keyword(s):

Behavioral Phenotype ◽

Oculocerebrorenal Syndrome

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Control of actin polymerization via the coincidence of phosphoinositides and high membrane curvature

The Journal of Cell Biology ◽

10.1083/jcb.201704061 ◽

2017 ◽

Vol 216 (11) ◽

pp. 3745-3765 ◽

Cited By ~ 46

Author(s):

Frederic Daste ◽

Astrid Walrant ◽

Mikkel R. Holst ◽

Jonathan R. Gadsby ◽

Julia Mason ◽

...

Keyword(s):

Mammalian Cells ◽

Actin Polymerization ◽

Kinase Inhibitors ◽

Mammalian Cell Culture ◽

Membrane Curvature ◽

Coated Pits ◽

Bar Domain ◽

Oculocerebrorenal Syndrome ◽

Cascade Amplification ◽

Hydrolysis Of

The conditional use of actin during clathrin-mediated endocytosis in mammalian cells suggests that the cell controls whether and how actin is used. Using a combination of biochemical reconstitution and mammalian cell culture, we elucidate a mechanism by which the coincidence of PI(4,5)P2 and PI(3)P in a curved vesicle triggers actin polymerization. At clathrin-coated pits, PI(3)P is produced by the INPP4A hydrolysis of PI(3,4)P2, and this is necessary for actin-driven endocytosis. Both Cdc42⋅guanosine triphosphate and SNX9 activate N-WASP–WIP- and Arp2/3-mediated actin nucleation. Membrane curvature, PI(4,5)P2, and PI(3)P signals are needed for SNX9 assembly via its PX–BAR domain, whereas signaling through Cdc42 is activated by PI(4,5)P2 alone. INPP4A activity is stimulated by high membrane curvature and synergizes with SNX9 BAR domain binding in a process we call curvature cascade amplification. We show that the SNX9-driven actin comets that arise on human disease–associated oculocerebrorenal syndrome of Lowe (OCRL) deficiencies are reduced by inhibiting PI(3)P production, suggesting PI(3)P kinase inhibitors as a therapeutic strategy in Lowe syndrome.

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