Whole Exome Sequencing in Brazilian Children and Adolescents with Steroid Resistant Nephrotic Syndrome

• Grant number: 15/20502-6
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2016
• End date: July 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Maricilda Palandi de Mello
• Grantee: Maricilda Palandi de Mello
• Host Institution: Centro de Biologia Molecular e Engenharia Genética (CBMEG). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Anna Cristina Gervasio de Britto Lutaif ; Gil Guerra Júnior ; Mara Sanches Guaragna ; Vera Maria Santoro Belangero

Abstract

Nephrotic Syndrome (NS) affects 16 in 100,000 children, making this condition one of the most common kidney diseases in childhood. The disease is usually classified as Congenital (CNS) when it manifests in utero or during the first three months of life, Infantile when the event occurs during the first year of life, in Childhood when symptoms occur between one year and 12 years and Juvenile, with onset between 12 and 18 years old. Approximately 20% of children with nephrotic syndrome are resistant to steroids and other immunosuppressors and are classified as Steroid Resistant (SRNS); the remaining 80% are Steroid Sensitive (SSNS). The main renal histology detected is focal segmental glomerulosclerosis (FSGS). The main cause of clinical manifestations is a dysfunction of the renal glomerular filtration barrier (GFB) leading to a massive loss of essential proteins in the urine. NS is a clinically and genetically heterogeneous disease with more than 20 genes already identified as being responsible for the etiology of a large proportion of SRNS cases. Our group has already screened the three main genes (NPHS2, NPHS1 and WT1) in 150 children using Sanger sequencing methodology. Mutations that correspond to the clinic symptoms were identified in only 10 patients (6.7%). The next step will be the establishment of Whole Exome Sequencing methodology to search for mutations in other genes to elucidate some cases that have still remained unclear. This project will bring further advances in the knowledge on the still incipient field of NS genetics in Brazil. We intend to implement and establish the high-throughput sequencing method starting with NS to gain skills in this methodology and then extend its application for the study of other important conditions in our laboratory. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

WATANABE, ANDREIA; GUARAGNA, MARA SANCHES; SANTORO BELANGERO, VERA MARIA; SERAFIM CASIMIRO, FERNANDA MARIA; PESQUERO, JOAO BOSCO; FELTRAN, LUCIANA DE SANTIS; PEREIRA PALMA, LILIAN MONTEIRO; VARELA, PATRICIA; MIRANDA DE MENEZES NEVES, PRECIL DIEGO; LERARIO, ANTONIO MARCONDES; et al. APOL1 in an ethnically diverse pediatric population with nephrotic syndrome: implications in focal segmental glomerulosclerosis and other diagnoses. Pediatric Nephrology, v. 36, n. 8, SI, p. 2327-2336, AUG 2021. (13/02162-8, 14/27198-8, 15/20502-6)

GUARAGNA, MARA SANCHES; DE BRITO LUTAIF, ANNA CRISTINA GERVASIO; DE SOUZA, MARCELA LOPES; MACIEL-GUERRA, ANDREA TREVAS; BELANGERO, VERA MARIA SANTORO; GUERRA-JUNIOR, GIL; DE MELLO, MARICILDA PALANDI. Promises and pitfalls of whole-exome sequencing exemplified by a nephrotic syndrome family. Molecular Genetics and Genomics, v. 295, n. 1, p. 135-142, JAN 2020. (13/24088-4, 15/20502-6)

GUARAGNA, MARA SANCHES; LEDESMA, FELIPE LOURENCO; MANZANO, VICTORIA ZAVANELLI; MACIEL-GUERRA, ANDREA TREVAS; GUERRA-JUNIOR, GIL; SILVA, MARCELO MILONE; DE BRITO, PEDRO LUIZ; DE MELLO, MARICILDA PALANDI. Bilateral Wilms' tumor in a child with Denys-Drash syndrome: novel frameshift variant disrupts the WT1 nuclear location signaling region. JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM, v. 35, n. 6, p. 7-pg., 2022-03-21. (15/20502-6)