Academic Journal
Reverse phenotyping after whole-Exome sequencing in steroid-resistant nephrotic syndrome
| العنوان: | Reverse phenotyping after whole-Exome sequencing in steroid-resistant nephrotic syndrome |
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| المؤلفون: | Landini S., Mazzinghi B., Becherucci F., Allinovi M., Provenzano A., Palazzo V., Ravaglia F., Artuso R., Bosi E., Stagi S., Sansavini G., Guzzi F., Cirillo L., Vaglio A., Murer L., Peruzzi L., Pasini A., Materassi M., Roperto R. M., Anders H. -J., Rotondi M., Giglio S. R., Romagnani P. |
| المساهمون: | Landini, S., Mazzinghi, B., Becherucci, F., Allinovi, M., Provenzano, A., Palazzo, V., Ravaglia, F., Artuso, R., Bosi, E., Stagi, S., Sansavini, G., Guzzi, F., Cirillo, L., Vaglio, A., Murer, L., Peruzzi, L., Pasini, A., Materassi, M., Roperto, R. M., Anders, H. -J., Rotondi, M., Giglio, S. R., Romagnani, P. |
| سنة النشر: | 2020 |
| المجموعة: | Università degli Studi di Cagliari: UNICA IRIS |
| مصطلحات موضوعية: | United State, Chronic kidney disease, Chronic renal insufficiency, Genetic testing, Human, Medical genetic, Multiple drug resistance, Nephrotic syndrome, Phenotype, Retrospective studie, Steroid, Whole exome sequencing, Workflow |
| الوصف: | Background and objectives Nephrotic syndrome is a typical presentation of genetic podocytopathies but occasionally other genetic nephropathies can present as clinically indistinguishable phenocopies. We hypothesized that extended genetic testing followed by reverse phenotyping would increase the diagnostic rate for these patients. Design, setting, participants, & measurements All patients diagnosed with nephrotic syndrome and referred to our center between 2000 and 2018 were assessed in this retrospective study. When indicated, whole-exome sequencing and in silico filtering of 298 genes related to CKD were combined with subsequent reverse phenotyping in patients and families. Pathogenic variants were defined according to current guidelines of the American College of Medical Genetics. Results A total of 111 patients (64 steroid-resistant and 47 steroid-sensitive) were included in the study. Not a single pathogenic variant was detected in the steroid-sensitive group. Overall, 30% (19 out of 64) of steroid-resistant patients had pathogenic variants in podocytopathy genes, whereas a substantial number of variants were identified in other genes, not commonly associated with isolated nephrotic syndrome. Reverse phenotyping, on the basis of a personalized diagnostic workflow, permitted to identify previously unrecognized clinical signs of an unexpected underlying genetic nephropathy in a further 28% (18 out of 64) of patients. These patients showed similar multidrug resistance, but different long-term outcome, when compared with genetic podocytopathies. Conclusions Reverse phenotyping increased the diagnostic accuracy in patients referred with the diagnosis of steroid-resistant nephrotic syndrome. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/31831576; info:eu-repo/semantics/altIdentifier/wos/WOS:000510213000014; volume:15; issue:1; firstpage:89; lastpage:100; numberofpages:12; journal:CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; http://hdl.handle.net/11584/297993 |
| DOI: | 10.2215/CJN.06060519 |
| الاتاحة: | http://hdl.handle.net/11584/297993 https://doi.org/10.2215/CJN.06060519 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.56DED519 |
| قاعدة البيانات: | BASE |
| DOI: | 10.2215/CJN.06060519 |
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