Anthony J Bleyer1, Maggie Westemeyer2, Jing Xie2, Michelle S Bloom3, Katya Brossart2, Jason J Eckel4, Frederick Jones4, Miklos Z Molnar5, Wayne Kotzker6, Prince Anand7, Stanislav Kmoch1,8, Yuan Xue9, Samuel Strom9, Sumit Punj2, Zachary P Demko2, Hossein Tabriziani2, Paul R Billings2, Trudy McKanna2. 1. Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. 2. Natera, Inc., San Carlos, California, USA. 3. Natera, Inc., San Carlos, California, USA, mbloom@natera.com. 4. North Carolina Nephrology Associates, Cary, North Carolina, USA. 5. Division of Nephrology & Hypertension, Department of Medicine, University of Utah, Salt Lake City, Utah, USA. 6. Florida Kidney Physicians, Boca Raton, Florida, USA. 7. MUSC Lancaster, Lancaster, South Carolina, USA. 8. Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, Prague, Czechia. 9. Fulgent Genetics, Temple City, California, USA.
Abstract
INTRODUCTION: Chronic kidney disease (CKD) is a major public health issue in the USA. Identification of monogenic causes of CKD, which are present in ∼10% of adult cases, can impact prognosis and patient management. Broad gene panels can provide unbiased testing approaches, which are advantageous in phenotypically heterogeneous diseases. However, the use and yield of broad genetic panels by nephrologists in clinical practice is not yet well characterized. METHODS: Renal genetic testing, ordered exclusively for clinical purposes, predominantly by general and transplant nephrologists within the USA, was performed on 1,007 consecutive unique patient samples. Testing was performed using a commercially available next-generation sequencing-based 382 gene kidney disease panel. Pathogenic (P) and likely pathogenic (LP) variants were reported. Positive findings included a monoallelic P/LP variant in an autosomal dominant or X-linked gene and biallelic P/LP variants in autosomal recessive genes. RESULTS: Positive genetic findings were identified in 21.1% (212/1,007) of cases. A total of 220 positive results were identified across 48 genes. Positive results occurred most frequently in the PKD1 (34.1%), COL4A5 (10.9%), PKD2 (10.0%), COL4A4 (6.4%), COL4A3 (5.9%), and TTR (4.1%) genes. Variants identified in the remaining 42 genes comprised 28.6% of the total positive findings, including single positive results in 26 genes. Positive results in >1 gene were identified in 7.5% (16/212) of cases. CONCLUSIONS: Use of broad panel genetic testing by clinical nephrologists had a high success rate, similar to results obtained by academic centers specializing in genetics.
INTRODUCTION: Chronic kidney disease (CKD) is a major public health issue in the USA. Identification of monogenic causes of CKD, which are present in ∼10% of adult cases, can impact prognosis and patient management. Broad gene panels can provide unbiased testing approaches, which are advantageous in phenotypically heterogeneous diseases. However, the use and yield of broad genetic panels by nephrologists in clinical practice is not yet well characterized. METHODS: Renal genetic testing, ordered exclusively for clinical purposes, predominantly by general and transplant nephrologists within the USA, was performed on 1,007 consecutive unique patient samples. Testing was performed using a commercially available next-generation sequencing-based 382 gene kidney disease panel. Pathogenic (P) and likely pathogenic (LP) variants were reported. Positive findings included a monoallelic P/LP variant in an autosomal dominant or X-linked gene and biallelic P/LP variants in autosomal recessive genes. RESULTS: Positive genetic findings were identified in 21.1% (212/1,007) of cases. A total of 220 positive results were identified across 48 genes. Positive results occurred most frequently in the PKD1 (34.1%), COL4A5 (10.9%), PKD2 (10.0%), COL4A4 (6.4%), COL4A3 (5.9%), and TTR (4.1%) genes. Variants identified in the remaining 42 genes comprised 28.6% of the total positive findings, including single positive results in 26 genes. Positive results in >1 gene were identified in 7.5% (16/212) of cases. CONCLUSIONS: Use of broad panel genetic testing by clinical nephrologists had a high success rate, similar to results obtained by academic centers specializing in genetics.
Authors: Sneh Lata; Maddalena Marasa; Yifu Li; David A Fasel; Emily Groopman; Vaidehi Jobanputra; Hila Rasouly; Adele Mitrotti; Rik Westland; Miguel Verbitsky; Jordan Nestor; Lindsey M Slater; Vivette D'Agati; Marcin Zaniew; Anna Materna-Kiryluk; Francesca Lugani; Gianluca Caridi; Luca Rampoldi; Aditya Mattoo; Chad A Newton; Maya K Rao; Jai Radhakrishnan; Wooin Ahn; Pietro A Canetta; Andrew S Bomback; Gerald B Appel; Corinne Antignac; Glen S Markowitz; Christine K Garcia; Krzysztof Kiryluk; Simone Sanna-Cherchi; Ali G Gharavi Journal: Ann Intern Med Date: 2017-12-05 Impact factor: 25.391
Authors: Dervla M Connaughton; Claire Kennedy; Shirlee Shril; Nina Mann; Susan L Murray; Patrick A Williams; Eoin Conlon; Makiko Nakayama; Amelie T van der Ven; Hadas Ityel; Franziska Kause; Caroline M Kolvenbach; Rufeng Dai; Asaf Vivante; Daniela A Braun; Ronen Schneider; Thomas M Kitzler; Brona Moloney; Conor P Moran; John S Smyth; Alan Kennedy; Katherine Benson; Caragh Stapleton; Mark Denton; Colm Magee; Conall M O'Seaghdha; William D Plant; Matthew D Griffin; Atif Awan; Clodagh Sweeney; Shrikant M Mane; Richard P Lifton; Brenda Griffin; Sean Leavey; Liam Casserly; Declan G de Freitas; John Holian; Anthony Dorman; Brendan Doyle; Peter J Lavin; Mark A Little; Peter J Conlon; Friedhelm Hildebrandt Journal: Kidney Int Date: 2019-02-14 Impact factor: 10.612
Authors: Emily E Groopman; Maddalena Marasa; Sophia Cameron-Christie; Slavé Petrovski; Vimla S Aggarwal; Hila Milo-Rasouly; Yifu Li; Junying Zhang; Jordan Nestor; Priya Krithivasan; Wan Yee Lam; Adele Mitrotti; Stacy Piva; Byum H Kil; Debanjana Chatterjee; Rachel Reingold; Drew Bradbury; Michael DiVecchia; Holly Snyder; Xueru Mu; Karla Mehl; Olivia Balderes; David A Fasel; Chunhua Weng; Jai Radhakrishnan; Pietro Canetta; Gerald B Appel; Andrew S Bomback; Wooin Ahn; Natalie S Uy; Shumyle Alam; David J Cohen; Russell J Crew; Geoffrey K Dube; Maya K Rao; Sitharthan Kamalakaran; Brett Copeland; Zhong Ren; Joshua Bridgers; Colin D Malone; Caroline M Mebane; Neha Dagaonkar; Bengt C Fellström; Carolina Haefliger; Sumit Mohan; Simone Sanna-Cherchi; Krzysztof Kiryluk; Jan Fleckner; Ruth March; Adam Platt; David B Goldstein; Ali G Gharavi Journal: N Engl J Med Date: 2018-12-26 Impact factor: 176.079
Authors: Michal Mrug; Michelle S Bloom; Christine Seto; Meenakshi Malhotra; Hossein Tabriziani; Philippe Gauthier; Vicki Sidlow; Trudy McKanna; Paul R Billings Journal: Kidney Med Date: 2021-10-05
Authors: Uyenlinh L Mirshahi; Ahana Bhan; Lotte E Tholen; Brian Fang; Guoli Chen; Bryn Moore; Adam Cook; Prince Mohan Anand; Kashyap Patel; Mary E Haas; Luca A Lotta; Peter Igarashi; Jeroen H F de Baaij; Silvia Ferrè; Joost G J Hoenderop; David J Carey; Alexander R Chang Journal: Kidney Int Rep Date: 2022-07-07