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Ke Ning, Emilie Song, Kathryn M. Haider, Alireza Ghaffarieh, Jorge A. Alvarado, Yang Sun; Ocular and renal phenotypes of NPHP1 deletion in Senior Loken syndrome. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5401.
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Nephronophthisis (NPHP) is an inherited autosomal-recessive disease that presents with renal and ocular manifestations. NPHP patients may develop ocular phenotypes of ocular motor apraxia and retinitis pigmentosa. The prevailing cause of NPHP is homozygous deletion in NPHP1 gene, named juvenile nephronophthisis type 1. Disruptions in formation of NPHP complex may result in abnormal primary cilia formation. Recently phosphoinositides have become recognized as a critical component of ciliary membrane. The purpose of this study is to report the clinical findings of a nephronophthisis patient and to determine the distribution of phosphoinositide 5-phosphatases in the patient-derived cilia.
A 10-year-old boy was diagnosed with juvenile nephronophthisis and Senior Loken syndrome based on the clinical manifestations and sequencing analysis performed by Athena Diagnostics, MA. Electroretinogram (ERG) and Humphrey visual field were implemented to evaluate visual functions. Hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) were conducted on renal samples to investigate presence of primary cilia. Immunofluorescence staining of kidney cilia was performed using anti phosphoinositide 5-phosphatases (OCRL and INPP5E).
ERG showed reduced amplitude of both A and B waves affecting predominant rod with preservation of cone function. Renal histology showed a characteristic triad of corticomedullary cysts, tubular basement membrane disruption, and tubulointerstitial nephropathy, consistent with junvenile nephrophthisis. TEM revealed thickened tubular membrane and decreased cilia. Immunofluorescence imaging showed disorganized cilia in renal tubular cells and aberrant expression of phosphoinositide 5-phosphatases.
NPHP1 deletion can result in both ocular and renal manifestations. This is the first report of the patient-derived cilia, obtained from renal samples, which showed disorganized cilia morphology and decreased expression of phosphoinositide 5-phosphatases compared with normal controls, suggesting that NPHP1 may play a role in controlling phosphoinositide 5-phosphatases in cilia.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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