Jinal M Thakor1, Glory Parmar1, Kinnari N Mistry2, Sishir Gang3, Dharamshibhai N Rank4, Chaitanya G Joshi5. 1. Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences, ADIT Campus, New Vallabh Vidyanagar, 388121, Anand, Gujarat, India. 2. Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences, ADIT Campus, New Vallabh Vidyanagar, 388121, Anand, Gujarat, India. kinnarimistry@aribas.edu.in. 3. Muljibhai Patel Urological Hospital, Dr. V.V. Desai Road, Nadiad, 387001, Gujarat, India. 4. Department of Animal Breeding and Genetics, College of Veterinary Sciences and Animal Husbandry, Anand Agricultural University, Anand, 388110, Gujarat, India. 5. Department of Animal Biotechnology, College of Veterinary Sciences and Animal Husbandry, Anand Agricultural University, Anand, 388110, Gujarat, India.
Abstract
BACKGROUND: Nephrotic syndrome appears as a group of symptoms like proteinuria, edema and hyperlipidemia. Identification of monogenic forms revealed the physiology and pathogenesis of the SRNS. METHODS AND RESULTS: We performed Illumina panel sequencing of seven genes in 90 Indian patients to determine the role of these genetic mutations in nephrotic syndrome prognosis. Samtool was used for variants calling, and SnpEff and Snpsift did variants annotation. Clinical significance and variant classification were performed by the ClinVar database. In SSNS and SRNS patients, we found 0.78% pathogenic and 3.41% likely pathogenic mutations. Pathogenic mutations were found in LAMB2, LMX1B and WT1 genes, while likely pathogenic mutations were found in (6/13) LAMB2, (2/13) LMX1B, (2/13) TRPC6, (2/13) PTPRO and (1/13) PMM2 genes. Approximately 46% likely pathogenic mutations were contributed to the LAMB2 gene in SSNS and SRNS patients. We also detect 30 VUS (variants of uncertain significance), which were found (17/30) pathogenic and (13/30) likely pathogenic by different prediction tools. CONCLUSIONS: Multigene panels were used for genetic screening of heterogeneous disorders like nephrotic syndrome in the Indian population. We found pathogenic, likely pathogenic and certain VUS, which were responsible for the pathogenesis of the disease. Therefore, mutational analysis of SSNS and SRNS is necessary to avoid adverse effects of corticosteroids, modify the intensity of immunosuppressing agents, and prevent the disease's progression.
BACKGROUND: Nephrotic syndrome appears as a group of symptoms like proteinuria, edema and hyperlipidemia. Identification of monogenic forms revealed the physiology and pathogenesis of the SRNS. METHODS AND RESULTS: We performed Illumina panel sequencing of seven genes in 90 Indian patients to determine the role of these genetic mutations in nephrotic syndrome prognosis. Samtool was used for variants calling, and SnpEff and Snpsift did variants annotation. Clinical significance and variant classification were performed by the ClinVar database. In SSNS and SRNS patients, we found 0.78% pathogenic and 3.41% likely pathogenic mutations. Pathogenic mutations were found in LAMB2, LMX1B and WT1 genes, while likely pathogenic mutations were found in (6/13) LAMB2, (2/13) LMX1B, (2/13) TRPC6, (2/13) PTPRO and (1/13) PMM2 genes. Approximately 46% likely pathogenic mutations were contributed to the LAMB2 gene in SSNS and SRNS patients. We also detect 30 VUS (variants of uncertain significance), which were found (17/30) pathogenic and (13/30) likely pathogenic by different prediction tools. CONCLUSIONS: Multigene panels were used for genetic screening of heterogeneous disorders like nephrotic syndrome in the Indian population. We found pathogenic, likely pathogenic and certain VUS, which were responsible for the pathogenesis of the disease. Therefore, mutational analysis of SSNS and SRNS is necessary to avoid adverse effects of corticosteroids, modify the intensity of immunosuppressing agents, and prevent the disease's progression.
Authors: Rainer G Ruf; Michael Schultheiss; Anne Lichtenberger; Stephanie M Karle; Isabella Zalewski; Bettina Mucha; Anne Schulze Everding; Thomas Neuhaus; Ludwig Patzer; Christian Plank; Johannes P Haas; Fatih Ozaltin; Anita Imm; Arno Fuchshuber; Aysin Bakkaloglu; Friedhelm Hildebrandt Journal: Kidney Int Date: 2004-08 Impact factor: 10.612
Authors: Alberto Zagury; Anne Louise de Oliveira; Jose Augusto Araujo Montalvão; Regina Helena Leite Novaes; Vinicius Martins de Sá; Carlos Augusto Pinheiro de Moraes; Marcelo de Sousa Tavares Journal: J Bras Nefrol Date: 2013 Jul-Sep