{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:14:54Z","timestamp":1788527694138,"version":"build-2803163510"},"reference-count":99,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Pediatric nephrology is shifting from broad phenotype-based labels toward molecularly defined, genotype-guided diagnosis and management. Childhood kidney disorders are enriched for monogenic causes, yet persistent microscopic hematuria, bilateral kidney cysts, steroid-resistant nephrotic syndrome, and thrombotic microangiopathy may represent shared endpoints of biologically distinct mechanisms. Using these four scenarios, this narrative review illustrates how structured phenotyping, pedigree analysis, biochemical evaluation, and appropriately selected genomic testing can establish etiology, revise diagnoses, and guide clinical decision-making. Molecular diagnosis may support early nephroprotection, prevent ineffective immunosuppression, reveal tumor or extrarenal risks, enable mechanism-based therapy, and optimize transplantation planning. It also enables cascade testing, reproductive counseling, presymptomatic evaluation of relatives, and safer assessment of living-related donors. Genomic findings, however, require clinical context. Variants must be evaluated against gene\u2013disease validity, inheritance, segregation, molecular mechanism, and phenotype, while variants of uncertain significance should not independently determine treatment or donor eligibility. Negative or inconclusive findings should prompt phenotypic reassessment, evaluation of analytical limitations, targeted studies, and periodic genomic reanalysis. Emerging genome and long-read sequencing, multiomics, artificial intelligence, and RNA-based therapeutics may further expand precision care, but rigorous interpretation, equitable access, appropriate counseling, and multidisciplinary collaboration remain essential. Precision nephrology derives value not from identifying variants alone, but from converting molecular etiology into safer, anticipatory, and individualized care.<\/jats:p>","DOI":"10.3390\/genes17091069","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T12:20:19Z","timestamp":1788524419000},"page":"1069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Precision Medicine in Pediatric Nephrology: From Shared Clinical Phenotypes to Genotype-Guided Diagnosis and Management"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5217-1766","authenticated-orcid":false,"given":"John","family":"Dotis","sequence":"first","affiliation":[{"name":"Third Department of Pediatrics, Hippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1618-9285","authenticated-orcid":false,"given":"Nikoleta","family":"Printza","sequence":"additional","affiliation":[{"name":"First Department of Pediatrics, Hippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1093\/ndt\/gfab218","article-title":"Genetic Testing in the Diagnosis of Chronic Kidney Disease: Recommendations for Clinical Practice","volume":"37","author":"Knoers","year":"2022","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1053\/j.ajkd.2024.05.011","article-title":"Clinical Genetic Testing in Nephrology: Core Curriculum 2024","volume":"84","author":"Aron","year":"2024","journal-title":"Am. J. Kidney Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/cge.13606","article-title":"Genetic Spectrum of Renal Disease for 1001 Chinese Children Based on a Multicenter Registration System","volume":"96","author":"Rao","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1056\/NEJMoa1806891","article-title":"Diagnostic Utility of Exome Sequencing for Kidney Disease","volume":"380","author":"Groopman","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1681\/ASN.2018060575","article-title":"Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients","volume":"30","author":"Mann","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dotis, J., and Fourikou, M. (2026). The Dawn of Precision Medicine in Pediatric Nephrology: Lumasiran and the Era of siRNA Therapies for Primary Hyperoxaluria Type 1. J. Pers. Med., 16.","DOI":"10.3390\/jpm16010015"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"D1207","DOI":"10.1093\/nar\/gkaa1043","article-title":"Human Phenotype Ontology in 2021","volume":"49","author":"Gargano","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41436-020-00963-4","article-title":"Clinical impact of genomic testing in patients with suspected monogenic kidney disease","volume":"23","author":"Jayasinghe","year":"2021","journal-title":"Genet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"106495","DOI":"10.1016\/j.ekir.2026.106495","article-title":"German Clinical Practice Guideline on Microhematuria in Children and Young Adults: Evaluating Early Detection of Kidney Disease","volume":"11","author":"Latta","year":"2026","journal-title":"Kidney Int. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/ndt\/gfae265","article-title":"Diagnosis, management and treatment of the Alport syndrome\u20142024 guideline on behalf of ERKNet, ERA and ESPN","volume":"40","author":"Torra","year":"2025","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s00467-024-06538-8","article-title":"Detection of Alport gene variants in children and young people with persistent haematuria","volume":"40","author":"Ng","year":"2025","journal-title":"Pediatr. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s00467-022-05627-w","article-title":"Variants in genes coding for collagen type IV \u03b1-chains are frequent causes of persistent, isolated hematuria during childhood","volume":"38","author":"Alge","year":"2023","journal-title":"Pediatr. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3625","DOI":"10.1007\/s00467-023-05993-z","article-title":"COL4A gene variants are common in children with hematuria and a family history of kidney disease","volume":"38","author":"Rheault","year":"2023","journal-title":"Pediatr. Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"143","DOI":"10.2215\/CJN.04230321","article-title":"Guidelines for genetic testing and management of Alport syndrome","volume":"17","author":"Savige","year":"2022","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"sfaf272","DOI":"10.1093\/ckj\/sfaf272","article-title":"Age at disease onset and risk of chronic kidney disease in patients with heterozygous disease-causing variants in COL4A3 and COL4A4","volume":"18","author":"Hu","year":"2025","journal-title":"Clin. Kidney J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1093\/ndt\/gfab334","article-title":"Heterozygous COL4A3\/COL4A4 mutations: The hidden part of the iceberg?","volume":"37","author":"Mastrangelo","year":"2022","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1007\/s00467-026-07185-x","article-title":"Redefining Alport syndrome in the era of genomic medicine: Time for a unified, genotype-driven nomenclature","volume":"41","author":"Dotis","year":"2026","journal-title":"Pediatr. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/S0140-6736(10)60670-8","article-title":"Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis","volume":"376","author":"Gale","year":"2010","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.2215\/CJN.09541010","article-title":"Familial C3 glomerulopathy associated with CFHR5 mutations: Clinical characteristics of 91 patients in 16 pedigrees","volume":"6","author":"Athanasiou","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1093\/ckj\/sfy117","article-title":"MYH9-related disorders display heterogeneous kidney involvement and outcome","volume":"12","author":"Tabibzadeh","year":"2019","journal-title":"Clin. Kidney J."},{"key":"ref_22","unstructured":"Adam, M.P., Bick, S., Mirzaa, G.M., Wallace, S.E., and Amemiya, A. (2008). MYH9-Related Disease. GeneReviews \u00ae, University of Washington. updated 18 February 2021."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1016\/j.kint.2019.12.015","article-title":"A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport\u2019s syndrome","volume":"97","author":"Gross","year":"2020","journal-title":"Kidney Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1007\/s00467-021-05040-9","article-title":"Genotype\u2013phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome","volume":"36","author":"Zhang","year":"2021","journal-title":"Pediatr. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Apetrii, M., Costache, A.D., Costache Enache, I.I., Voroneanu, L., Covic, A.S., Kanbay, M., and Covic, A. (2025). Complement system inhibitors in nephrology: An update\u2014Narrative review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125902"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1001\/jamapediatrics.2017.3938","article-title":"Perinatal Diagnosis, Management, and Follow-up of Cystic Renal Diseases: A Clinical Practice Recommendation With Systematic Literature Reviews","volume":"172","author":"Gimpel","year":"2018","journal-title":"JAMA Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1148\/radiol.2018181243","article-title":"Imaging of Kidney Cysts and Cystic Kidney Diseases in Children: An International Working Group Consensus Statement","volume":"290","author":"Gimpel","year":"2019","journal-title":"Radiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s00467-024-06548-6","article-title":"Matching Clinical and Genetic Data in Pediatric Patients at Risk of Developing Cystic Kidney Disease","volume":"40","author":"Vaisitti","year":"2025","journal-title":"Pediatr. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nrneph.2014.232","article-title":"HNF1B-Associated Renal and Extra-Renal Disease\u2014An Expanding Clinical Spectrum","volume":"11","author":"Clissold","year":"2015","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1681\/ASN.2008060633","article-title":"HNF1B Mutations Associate with Hypomagnesemia and Renal Magnesium Wasting","volume":"20","author":"Adalat","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1016\/j.ekir.2024.05.007","article-title":"Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions","volume":"9","author":"Richard","year":"2024","journal-title":"Kidney Int. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1111\/j.1523-1755.2005.00148.x","article-title":"Clinical Consequences of PKHD1 Mutations in 164 Patients with Autosomal-Recessive Polycystic Kidney Disease (ARPKD)","volume":"67","author":"Bergmann","year":"2005","journal-title":"Kidney Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.jpeds.2014.06.015","article-title":"Expert Recommendations for the Diagnosis and Management of Autosomal Recessive Polycystic Kidney Disease: Report of an International Conference","volume":"165","author":"Bissler","year":"2014","journal-title":"J. Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1053\/j.akdh.2023.01.005","article-title":"Autosomal Recessive Polycystic Kidney Disease: Diagnosis, Prognosis, and Management","volume":"30","author":"Burgmaier","year":"2023","journal-title":"Adv. Kidney Dis. Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1681\/ASN.2010101080","article-title":"Mutations in Multiple PKD Genes May Explain Early and Severe Polycystic Kidney Disease","volume":"22","author":"Bergmann","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/s41581-019-0155-2","article-title":"International Consensus Statement on the Diagnosis and Management of Autosomal Dominant Polycystic Kidney Disease in Children and Young People","volume":"15","author":"Gimpel","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"(2025). Kidney Disease: Improving Global Outcomes (KDIGO) ADPKD Work Group. KDIGO 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Kidney Int., 107, S1\u2013S239.","DOI":"10.1016\/j.kint.2024.07.009"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"36","DOI":"10.2215\/CJN.0000000000000022","article-title":"Tolvaptan for Children and Adolescents with Autosomal Dominant Polycystic Kidney Disease: Randomized Controlled Trial","volume":"18","author":"Mekahli","year":"2023","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ajhg.2021.11.016","article-title":"Monoallelic IFT140 Pathogenic Variants Are an Important Cause of the Autosomal Dominant Polycystic Kidney-Spectrum Phenotype","volume":"109","author":"Senum","year":"2022","journal-title":"Am. J. Hum. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1053\/j.ajkd.2024.10.009","article-title":"Clinical Spectrum and Prognosis of Atypical Autosomal Dominant Polycystic Kidney Disease Caused by Monoallelic Pathogenic Variants of IFT140","volume":"85","author":"Zagorec","year":"2025","journal-title":"Am. J. Kidney Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1053\/j.ajkd.2025.08.006","article-title":"Monoallelic IFT140 Variants Causing Childhood-Onset Autosomal Dominant Polycystic Kidney Disease","volume":"87","author":"Griffiths","year":"2026","journal-title":"Am. J. Kidney Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.ajhg.2012.03.006","article-title":"Mainzer\u2013Saldino Syndrome Is a Ciliopathy Caused by IFT140 Mutations","volume":"90","author":"Perrault","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s00467-011-1826-9","article-title":"HNF1B and PAX2 Mutations Are a Common Cause of Renal Hypodysplasia in the CKiD Cohort","volume":"26","author":"Thomas","year":"2011","journal-title":"Pediatr. Nephrol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s10038-020-0741-y","article-title":"Clinical and Genetic Variability of PAX2-Related Disorder in the Japanese Population","volume":"65","author":"Rossanti","year":"2020","journal-title":"J. Hum. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/s41431-025-01822-z","article-title":"Genotype of PAX2-Related Disorders Correlates with Kidney and Ocular Manifestations","volume":"33","author":"Kim","year":"2025","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1681\/ASN.2014050489","article-title":"A Single-Gene Cause in 29.5% of Cases of Steroid-Resistant Nephrotic Syndrome","volume":"26","author":"Sadowski","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1007\/s00467-020-04519-1","article-title":"IPNA Clinical Practice Recommendations for the Diagnosis and Management of Children with Steroid-Resistant Nephrotic Syndrome","volume":"35","author":"Trautmann","year":"2020","journal-title":"Pediatr. Nephrol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"592","DOI":"10.2215\/CJN.06260614","article-title":"Spectrum of Steroid-Resistant and Congenital Nephrotic Syndrome in Children: The PodoNet Registry Cohort","volume":"10","author":"Trautmann","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.kint.2016.10.013","article-title":"Genomic and Clinical Profiling of a National Nephrotic Syndrome Cohort Advocates a Precision Medicine Approach to Disease Management","volume":"91","author":"Bierzynska","year":"2017","journal-title":"Kidney Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1038\/s41431-020-0642-8","article-title":"Genetic Aspects of Congenital Nephrotic Syndrome: A Consensus Statement from the ERKNet\u2013ESPN Inherited Glomerulopathy Working Group","volume":"28","author":"Ozaltin","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/ki.2013.519","article-title":"Genotype\u2013Phenotype Associations in WT1 Glomerulopathy","volume":"85","author":"Lipska","year":"2014","journal-title":"Kidney Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1007\/s00467-008-0748-7","article-title":"Variable Phenotype of Pierson Syndrome","volume":"23","author":"Choi","year":"2008","journal-title":"Pediatr. Nephrol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/ki.2012.349","article-title":"Mutations in the INF2 Gene Account for a Significant Proportion of Familial but Not Sporadic Focal and Segmental Glomerulosclerosis","volume":"83","author":"Barua","year":"2013","journal-title":"Kidney Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.1172\/JCI69000","article-title":"ADCK4 Mutations Promote Steroid-Resistant Nephrotic Syndrome through CoQ10 Biosynthesis Disruption","volume":"123","author":"Ashraf","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.1007\/s00467-020-04914-8","article-title":"Primary Coenzyme Q10 Nephropathy, a Potentially Treatable Form of Steroid-Resistant Nephrotic Syndrome","volume":"36","author":"Tan","year":"2021","journal-title":"Pediatr. Nephrol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.2215\/CJN.19171220","article-title":"Genetic Basis of Type IV Collagen Disorders of the Kidney","volume":"16","author":"Quinlan","year":"2021","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Dotis, J., Kondou, A., Liapis, G., Ververi, A., Kollios, K., and Printza, N. (2026). When Genes Reveal the Truth: Alport Syndrome Mimicking Steroid-Resistant Nephrotic Syndrome. Pediatr. Rep., 18.","DOI":"10.3390\/pediatric18010003"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.2215\/CJN.05260610","article-title":"Clinical Utility of Genetic Testing in Children and Adults with Steroid-Resistant Nephrotic Syndrome","volume":"6","author":"Bullich","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s00467-017-3838-6","article-title":"Genetic Testing in Steroid-Resistant Nephrotic Syndrome: Why, Who, When and How?","volume":"34","author":"Preston","year":"2019","journal-title":"Pediatr. Nephrol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7","DOI":"10.23876\/j.krcp.20.001","article-title":"Genetic Tests in Children with Steroid-Resistant Nephrotic Syndrome","volume":"39","author":"Cheong","year":"2020","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1093\/ndt\/gfv355","article-title":"Genetic Testing in Steroid-Resistant Nephrotic Syndrome: When and How?","volume":"31","author":"Lovric","year":"2016","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2215\/CJN.07370715","article-title":"Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic versus Genetic Steroid-Resistant Nephrotic Syndrome","volume":"11","author":"Beck","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.kint.2022.04.029","article-title":"Oral Coenzyme Q10 Supplementation Leads to Better Preservation of Kidney Function in Steroid-Resistant Nephrotic Syndrome Due to Primary Coenzyme Q10 Deficiency","volume":"102","author":"Drovandi","year":"2022","journal-title":"Kidney Int."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00467-015-3076-8","article-title":"An International Consensus Approach to the Management of Atypical Hemolytic Uremic Syndrome in Children","volume":"31","author":"Loirat","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1007\/s00467-021-05370-8","article-title":"Thrombotic Microangiopathy in Children","volume":"37","author":"Palma","year":"2022","journal-title":"Pediatr. Nephrol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.2215\/CJN.02210310","article-title":"Relative Role of Genetic Complement Abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical Phenotype","volume":"5","author":"Noris","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.kint.2016.10.005","article-title":"Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy: Conclusions from a \u201cKidney Disease: Improving Global Outcomes\u201d (KDIGO) Controversies Conference","volume":"91","author":"Goodship","year":"2017","journal-title":"Kidney Int."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Bogdan, R.-G., Anderco, P., Ichim, C., Cimpean, A.-M., Todor, S.B., Glaja-Iliescu, M., Crainiceanu, Z.P., and Popa, M.L. (2025). Atypical Hemolytic Uremic Syndrome: A Review of Complement Dysregulation, Genetic Susceptibility and Multiorgan Involvement. J. Clin. Med., 14.","DOI":"10.3390\/jcm14072527"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1182\/blood-2018-11-884700","article-title":"Characterization and Treatment of Congenital Thrombotic Thrombocytopenic Purpura","volume":"133","author":"Alwan","year":"2019","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.3324\/haematol.2019.216796","article-title":"The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: Key Findings at Enrollment until 2017","volume":"104","author":"Sakai","year":"2019","journal-title":"Haematologica"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00467-016-3399-0","article-title":"Renal Thrombotic Microangiopathy in Patients with cblC Defect: Review of an Under-Recognized Entity","volume":"32","author":"Beck","year":"2017","journal-title":"Pediatr. Nephrol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.ekir.2018.05.015","article-title":"Cobalamin C Deficiency Induces a Typical Histopathological Pattern of Renal Arteriolar and Glomerular Thrombotic Microangiopathy","volume":"3","author":"Lemoine","year":"2018","journal-title":"Kidney Int. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/ng.2590","article-title":"Recessive Mutations in DGKE Cause Atypical Hemolytic-Uremic Syndrome","volume":"45","author":"Lemaire","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/j.kint.2020.01.045","article-title":"Long-Term Outcomes and Response to Treatment in Diacylglycerol Kinase Epsilon Nephropathy","volume":"97","author":"Brocklebank","year":"2020","journal-title":"Kidney Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1681\/ASN.2015101189","article-title":"Thrombotic Microangiopathy in Inverted Formin 2\u2013Mediated Renal Disease","volume":"28","author":"Challis","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1182\/blood.2022015583","article-title":"How I Treat Thrombotic Microangiopathy in the Era of Rapid Genomics","volume":"141","author":"Doreille","year":"2023","journal-title":"Blood"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.kint.2015.11.026","article-title":"Eculizumab Is a Safe and Effective Treatment in Pediatric Patients with Atypical Hemolytic Uremic Syndrome","volume":"89","author":"Greenbaum","year":"2016","journal-title":"Kidney Int."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.kint.2020.10.046","article-title":"The Long-Acting C5 Inhibitor, Ravulizumab, Is Effective and Safe in Pediatric Patients with Atypical Hemolytic Uremic Syndrome Na\u00efve to Complement Inhibitor Treatment","volume":"100","author":"Ariceta","year":"2021","journal-title":"Kidney Int."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1182\/blood.2020009280","article-title":"Eculizumab Discontinuation in Children and Adults with Atypical Hemolytic-Uremic Syndrome: A Prospective Multicenter Study","volume":"137","author":"Fakhouri","year":"2021","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1182\/blood.2022018833","article-title":"Atypical Hemolytic Uremic Syndrome in the Era of Terminal Complement Inhibition: An Observational Cohort Study","volume":"142","author":"Brocklebank","year":"2023","journal-title":"Blood"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1056\/NEJMoa2314793","article-title":"Recombinant ADAMTS13 in Congenital Thrombotic Thrombocytopenic Purpura","volume":"390","author":"Scully","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3711","DOI":"10.1016\/j.jtha.2025.06.002","article-title":"2025 Focused Update of the 2020 ISTH Guidelines for Management of Thrombotic Thrombocytopenic Purpura","volume":"23","author":"Zheng","year":"2025","journal-title":"J. Thromb. Haemost."},{"key":"ref_83","unstructured":"U.S. Food and Drug Administration (2026, July 31). Safety Labeling Change Order and Safety Labeling Change Notification Letter\u2014ADZYNMA (ADAMTS13, Recombinant-krhn), Available online: https:\/\/www.fda.gov\/media\/192821\/download."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.ajhg.2017.04.015","article-title":"Evaluating the Clinical Validity of Gene-Disease Associations: An Evidence-Based Framework Developed by the Clinical Genome Resource","volume":"100","author":"Strande","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/s41436-018-0391-z","article-title":"Patient re-contact after revision of genomic test results: Points to consider\u2014A statement of the American College of Medical Genetics and Genomics","volume":"21","author":"David","year":"2019","journal-title":"Genet. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/s41436-019-0478-1","article-title":"Points to consider in the reevaluation and reanalysis of genomic test results: A statement of the American College of Medical Genetics and Genomics","volume":"21","author":"Deignan","year":"2019","journal-title":"Genet. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1056\/NEJMoa2209046","article-title":"Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland","volume":"388","author":"Wright","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1056\/NEJMsa1507092","article-title":"Genetic Misdiagnoses and the Potential for Health Disparities","volume":"375","author":"Manrai","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ajhg.2015.05.022","article-title":"Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents","volume":"97","author":"Botkin","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"101454","DOI":"10.1016\/j.gim.2025.101454","article-title":"ACMG SF v3.3 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics","volume":"27","author":"Lee","year":"2025","journal-title":"Genet. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1056\/NEJMoa2314761","article-title":"Genome Sequencing for Diagnosing Rare Diseases","volume":"390","author":"Wojcik","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1056\/NEJMoa2035790","article-title":"100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care\u2014Preliminary Report","volume":"385","author":"Smedley","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s13073-023-01270-8","article-title":"Beyond the exome: Utility of long-read whole genome sequencing in exome-negative autosomal recessive diseases","volume":"15","author":"AlAbdi","year":"2023","journal-title":"Genome Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1126\/science.aar2131","article-title":"Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease","volume":"360","author":"Park","year":"2018","journal-title":"Science"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1038\/s41591-023-02401-9","article-title":"Integrated multi-omics for rapid rare disease diagnosis on a national scale","volume":"29","author":"Lunke","year":"2023","journal-title":"Nat. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"eaal5209","DOI":"10.1126\/scitranslmed.aal5209","article-title":"Improving genetic diagnosis in Mendelian disease with transcriptome sequencing","volume":"9","author":"Cummings","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/s42003-023-05203-4","article-title":"iPSC-derived type IV collagen \u03b15-expressing kidney organoids model Alport syndrome","volume":"6","author":"Hirayama","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"101402","DOI":"10.1016\/j.gim.2025.101402","article-title":"Calibration of additional computational tools expands ClinGen recommendation options for variant classification with PP3\/BP4 criteria","volume":"27","author":"Bergquist","year":"2025","journal-title":"Genet. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1186\/s13023-021-01872-8","article-title":"The European Rare Kidney Disease Registry (ERKReg): Objectives, design and initial results","volume":"16","author":"Bassanese","year":"2021","journal-title":"Orphanet J. 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