title: Heterogeneous genetic alterations in sporadic nephrotic syndrome associate with resistance to immunosuppression.
abstract: In children, sporadic nephrotic syndrome can be related to a genetic cause, but to what extent genetic alterations associate with resistance to immunosuppression is unknown. In this study, we designed a custom array for next-generation sequencing analysis of 19 target genes, reported as possible causes of nephrotic syndrome, in a cohort of 31 children affected by sporadic steroid-resistant nephrotic syndrome and 38 patients who exhibited a similar but steroid-sensitive clinical phenotype. Patients who exhibited extrarenal symptoms, had a familial history of the disease or consanguinity, or had a congenital onset were excluded. We identified a genetic cause in 32.3% of the children with steroid-resistant disease but zero of 38 children with steroid-sensitive disease. Genetic alterations also associated with lack of response to immunosuppressive agents in children with steroid-resistant disease (0% of patients with alterations versus 57.9% of patients without alterations responded to immunosuppressive agents), whereas clinical features, age at onset, and pathologic findings were similar in steroid-resistant patients with and without alterations. These results suggest that heterogeneous genetic alterations in children with sporadic forms of nephrotic syndrome associate with resistance to steroids as well as immunosuppressive treatments. In these patients, a comprehensive screening using such an array may, thus, be useful for genetic counseling and may help clinical decision making in a fast and cost-efficient manner.
authors: Department of Biomedical Experimental and Clinical Sciences "Mario Serio," and Medical Genetics and paola.romagnani@unifi.it s.giglio@meyer.it.
authors: Sabrina
authors: S
authors: Giglio
authors: Department of Biomedical Experimental and Clinical Sciences "Mario Serio," and.
authors: Aldesia
authors: A
authors: Provenzano
authors: Medical Genetics and.
authors: Benedetta
authors: B
authors: Mazzinghi
authors: Pediatric Nephrology Units, Meyer Children's University Hospital, Florence, Italy;
authors: Francesca
authors: F
authors: Becherucci
authors: Medical Genetics and.
authors: Laura
authors: L
authors: Giunti
authors: Pediatric Nephrology Units, Meyer Children's University Hospital, Florence, Italy;
authors: Giulia
authors: G
authors: Sansavini
authors: Pediatric Nephrology Units, Meyer Children's University Hospital, Florence, Italy;
authors: Fiammetta
authors: F
authors: Ravaglia
authors: Pediatric Nephrology Units, Meyer Children's University Hospital, Florence, Italy;
authors: Rosa Maria
authors: RM
authors: Roperto
authors: Pediatric Nephrology Units, Meyer Children's University Hospital, Florence, Italy;
authors: Silvia
authors: S
authors: Farsetti
authors: Department of Pediatrics, University of Padua, Padua, Italy; and.
authors: Elisa
authors: E
authors: Benetti
authors: Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri IRCCS, University of Pavia, Pavia, Italy.
authors: Mario
authors: M
authors: Rotondi
authors: Department of Pediatrics, University of Padua, Padua, Italy; and.
authors: Luisa
authors: L
authors: Murer
authors: Excellence Centre for Research, Transfer and High Education for the Development of DE NOVO Therapies (DENOTHE), University of Florence, Florence, Italy;
authors: Elena
authors: E
authors: Lazzeri
authors: Excellence Centre for Research, Transfer and High Education for the Development of DE NOVO Therapies (DENOTHE), University of Florence, Florence, Italy;
authors: Laura
authors: L
authors: Lasagni
authors: Pediatric Nephrology Units, Meyer Children's University Hospital, Florence, Italy;
authors: Marco
authors: M
authors: Materassi
authors: Department of Biomedical Experimental and Clinical Sciences "Mario Serio," and Pediatric Nephrology Units, Meyer Children's University Hospital, Florence, Italy; Excellence Centre for Research, Transfer and High Education for the Development of DE NOVO Therapies (DENOTHE), University of Florence, Florence, Italy; paola.romagnani@unifi.it s.giglio@meyer.it.
authors: Paola
authors: P
authors: Romagnani
mesh_terms: D000293:Adolescent; D000465:Algorithms; D000483:Alleles; D000818:Animals; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D020125:Mutation, Missense; D009404:Nephrotic Syndrome / Q000235:genetics*; D010641:Phenotype; D012189:Retrospective Studies; D013256:Steroids / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids
keywords: genetic variant; high-throughput DNA sequencing; immunosuppression; proteinuria