Immunofluorescence analyses of respiratory epithelial cells aid the diagnosis of nephronophthisis.
Background: Nephronophthisis (NPH) comprises a heterogeneous group of inherited renal ciliopathies clinically characterized by progressive kidney failure. So far, definite diagnosis is based on molecular testing only. Here, we studied the feasibility of NPHP1 and NPHP4 immunostaining of nasal epithe...
| Publicado en: | Pediatric Nephrology Vol. 39; no. 12; pp. 3471 - 3484 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Springer Nature
Dec2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=180501405&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 180501405 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0931041X EF1 jtl: Pediatric Nephrology issn: 0931041X maglogo: N pubinfo: dt: Dec2024 vid: 39 iid: 12 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 180501405 178803470 180501405 180501405 10.1007/s00467-024-06443-0 180501405 ppf: 3471 ppct: 13 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Immunofluorescence analyses of respiratory epithelial cells aid the diagnosis of nephronophthisis. aug: au: Hellmann, Carlotta Wohlgemuth, Kai Pennekamp, Petra George, Sebastian Dahmer-Heath, Mareike Konrad, Martin Omran, Heymut König, Jens Bergmann, C. Cetiner, M. Drube, J. Gimpel, C. Göbel, J. Haffner, D. Illig, T. Klopp, N. Liebau, M. C. Lienkamp, S. Okorn, C. Pape, L. affil: Department of General Pediatrics, University Children's Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany sug: subj: Polycystic Kidney, Autosomal Recessive Diagnosis Polycystic Kidney, Autosomal Recessive Familial and Genetic Epithelial Cells Respiratory System Fluorescent Antibody Technique Mutation Staining and Labeling Human Ciliopathies Microscopy Blotting, Western Descriptive Statistics Comparative Studies Genetics Nasal Mucosa Cell Culture Techniques Funding Source Carrier Proteins Signal Transduction Cytoskeletal Proteins Pilot Studies ab: Background: Nephronophthisis (NPH) comprises a heterogeneous group of inherited renal ciliopathies clinically characterized by progressive kidney failure. So far, definite diagnosis is based on molecular testing only. Here, we studied the feasibility of NPHP1 and NPHP4 immunostaining of nasal epithelial cells to secure and accelerate the diagnosis of NPH. Methods: Samples of 86 individuals with genetically determined renal ciliopathies were analyzed for NPHP1 localization using immunofluorescence microscopy (IF). A sub-cohort of 35 individuals was also analyzed for NPHP4 localization. Western blotting was performed to confirm IF results. Results: NPHP1 and NPHP4 were both absent in all individuals with disease-causing NPHP1 variants including one with a homozygous missense variant (c.1027G > A; p.Gly343Arg) formerly classified as a "variant of unknown significance." In individuals with an NPHP4 genotype, we observed a complete absence of NPHP4 while NPHP1 was severely reduced. IF results were confirmed by immunoblotting. Variants in other genes related to renal ciliopathies did not show any impact on NPHP1/NPHP4 expression. Aberrant immunostaining in two genetically unsolved individuals gave rise for a further genetic workup resulting in a genetic diagnosis for both with disease-causing variants in NPHP1 and NPHP4, respectively. Conclusions: IF of patient-derived respiratory epithelial cells may help to secure and accelerate the diagnosis of nephronophthisis—both by verifying inconclusive genetic results and by stratifying genetic diagnostic approaches. Furthermore, we provide in vivo evidence for the interaction of NPHP1 and NPHP4 in a functional module. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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