Abstract
Senior-Løken syndrome is a rare genetic disorder which presents with
nephronophthisis and retinal degeneration, leading to end-stage renal
disease and progressive blindness. The most frequent cause of juvenile
nephronophthisis is mutation in the nephronophthisis type 1 (NPHP1)
gene. NPHP1 encodes the protein nephrocystin-1, which functions at the
transition zone (TZ) of primary cilia. Here we report a 9-year-old
Senior-Løken syndrome patient with NPHP1 deletion, who presents with a
decreased electroretinogram consistent with early retinal degeneration.
The patient had undergone bilateral nephrectomy and a renal transplant.
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-phosphatases (INPP5E) showed loss of staining
compared to a healthy control. 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 in the ciliary membrane of renal
tubular cells.