Ocular Pathology of Oculocerebrorenal Syndrome of Lowe: Novel Mutations and Genotype-Phenotype Analysis

Emilie Song, Na Luo, Jorge A. Alvarado, Maria Lim, Cathleen Walnuss, Daniel Neely, Dan Spandau, Alireza Ghaffarieh, Yang Sun

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Mutations in the OCRL1 gene result in the oculocerebrorenal syndrome of Lowe, with symptoms including congenital bilateral cataracts, glaucoma, renal failure, and neurological impairments. OCRL1 encodes an inositol polyphosphate 5-phosphatase which preferentially dephosphorylates phosphatidylinositide 4,5 bisphosphate (PI(4,5)P2). We have identified two novel mutations in two unrelated Lowe syndrome patients with congenital glaucoma. Novel deletion mutations are detected at c.739-742delAAAG in Lowe patient 1 and c.1595-1631del in Lowe patient 2. End stage glaucoma in patient 2 resulted in the enucleation of the eye, which on histology demonstrated corneal keloid, fibrous infiltration of the angle, ectropion uvea, retinal gliosis, and retinal ganglion cell loss. We measured OCRL protein levels in patient keratinocytes and found that Lowe 1 patient cells had significantly reduced OCRL protein as compared to the control keratinocytes. Genotype-phenotype correlation of OCRL1 mutations associated with congenital glaucoma revealed clustering of missense and deletion mutations in the 5-phosphatase domain and the RhoGAP-like domain. In conclusion, we report novel OCRL1 mutations in Lowe syndrome patients and the corresponding histopathologic analysis of one patient's ocular pathology.

Original languageEnglish (US)
Article number1442
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Oculocerebrorenal Syndrome
Genotype
Pathology
Phenotype
Mutation
Glaucoma
Sequence Deletion
Keratinocytes
Eye Enucleation
Uvea
Ectropion
Keloid
Gliosis
Retinal Ganglion Cells
Genetic Association Studies
Missense Mutation
Phosphoric Monoester Hydrolases
Cataract
Renal Insufficiency
Cluster Analysis

ASJC Scopus subject areas

  • General

Cite this

Ocular Pathology of Oculocerebrorenal Syndrome of Lowe : Novel Mutations and Genotype-Phenotype Analysis. / Song, Emilie; Luo, Na; Alvarado, Jorge A.; Lim, Maria; Walnuss, Cathleen; Neely, Daniel; Spandau, Dan; Ghaffarieh, Alireza; Sun, Yang.

In: Scientific Reports, Vol. 7, No. 1, 1442, 01.12.2017.

Research output: Contribution to journalArticle

Song, Emilie ; Luo, Na ; Alvarado, Jorge A. ; Lim, Maria ; Walnuss, Cathleen ; Neely, Daniel ; Spandau, Dan ; Ghaffarieh, Alireza ; Sun, Yang. / Ocular Pathology of Oculocerebrorenal Syndrome of Lowe : Novel Mutations and Genotype-Phenotype Analysis. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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