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Defective INPP5E distribution in NPHP1‐related Senior–Loken syndrome
- Source :
- Molecular Genetics & Genomic Medicine, Molecular Genetics & Genomic Medicine, Vol 9, Iss 1, Pp n/a-n/a (2021)
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- 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.<br />In this study, we report a 9‐year‐old Senior‐Loken syndrome patient with NPHP1 deletion. We found the decreased expression of INPP5E specifically in the primary cilium, coupled with disorganized cilia morphology, suggests a novel role of NPHP1 in regulating ciliary phosphoinositide composition in the ciliary membrane of renal tubular cells.
- Subjects :
- Male
0301 basic medicine
Retinal degeneration
Pathology
medicine.medical_specialty
government.form_of_government
Leber Congenital Amaurosis
INPP5E
Senior–Loken syndrome
QH426-470
030105 genetics & heredity
Senior–Løken syndrome
Kidney
03 medical and health sciences
primary cilia
Optic Atrophies, Hereditary
Nephronophthisis
Genetics
medicine
Humans
Juvenile nephronophthisis
Cilia
Child
Molecular Biology
Ciliary membrane
Genetics (clinical)
Adaptor Proteins, Signal Transducing
NPHP1
business.industry
Cilium
Original Articles
Kidney Diseases, Cystic
medicine.disease
Ciliopathies
Phosphoric Monoester Hydrolases
Cytoskeletal Proteins
030104 developmental biology
medicine.anatomical_structure
transition zone
government
Original Article
business
Gene Deletion
Immunostaining
Subjects
Details
- ISSN :
- 23249269
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Molecular Genetics & Genomic Medicine
- Accession number :
- edsair.doi.dedup.....9c1e93a06ca73f49aedebcb149f20120
- Full Text :
- https://doi.org/10.1002/mgg3.1566