Open AccessDefective INPP5E distribution in NPHP1‐related Senior–Loken syndrome
Author(s) -
Ning Ke,
Song Emilie,
Sendayen Brent E.,
Prosseda Philipp P.,
Chang KunChe,
Ghaffarieh Alireza,
Alvarado Jorge A.,
Wang Biao,
Haider Kathryn M.,
Berbari Nicolas F.,
Hu Yang,
Sun Yang
Publication year - 2021
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1566
Subject(s) - nephronophthisis , cilium , biology , pathology , cystic kidney disease , kidney , retinal degeneration , medicine , endocrinology , microbiology and biotechnology , retinal , genetics , phenotype , biochemistry , gene
Background Senior–Loken syndrome is a rare genetic disorder that presents with nephronophthisis and retinal degeneration, leading to end‐stage renal disease and progressive blindness. The most frequent cause of juvenile nephronophthisis is a mutation in the nephronophthisis type 1 (NPHP1) gene. NPHP1 encodes the protein nephrocystin‐1, which functions at the transition zone (TZ) of primary cilia. Methods We report a 9‐year‐old Senior–Loken syndrome boy with NPHP1 deletion, who presents with bilateral vision decrease and cystic renal disease. Renal function deteriorated to require bilateral nephrectomy and renal transplant. We performed immunohistochemistry, H&E staining, and electron microscopy on the renal sample to determine the subcellular distribution of ciliary proteins in the absence of NPHP1. Results Immunohistochemistry and electron microscopy of the resected kidney showed disorganized cystic structures with loss of cilia in renal tubules. Phosphoinositides have been recently recognized as critical components of the ciliary membrane and immunostaining of kidney sections for phosphoinositide 5‐phosphatase, INPP5E, showed loss of staining compared to healthy control. Ophthalmic examination showed decreased electroretinogram consistent with early retinal degeneration. Conclusion The decreased expression of INPP5E specifically in the primary cilium, coupled with disorganized cilia morphology, suggests a novel role of NPHP1 that it is involved in regulating ciliary phosphoinositide composition in the ciliary membrane of renal tubular cells.