High-Throughput Genetic Testing for Thrombotic Microangiopathies and C3 Glomerulopathies
| Autor: | Michael J. Schnieders, Jill Hauer, Fengxiao Bu, Hela Azaiez, Nicole C. Meyer, Erika Takanami, Elizabeth A. Black-Ziegelbein, Nicolò Borsa, Christie P. Thomas, Kathy L. Frees, Michael N. Jones, Diana L. Kolbe, Yingyue Li, Carla Nishimura, Carla M. Nester, Richard J.H. Smith |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Thrombotic microangiopathy Adolescent Kidney Glomerulus Thrombotic thrombocytopenic purpura Context (language use) Biology Bioinformatics 03 medical and health sciences Clinical Research Atypical hemolytic uremic syndrome medicine Humans Genetic Testing Child Genetic testing Genetics Massive parallel sequencing medicine.diagnostic_test Thrombotic Microangiopathies CD46 Complement C3 General Medicine medicine.disease 030104 developmental biology Nephrology Child Preschool Female Kidney Diseases CFHR5 |
| Zdroj: | Journal of the American Society of Nephrology. 27:1245-1253 |
| ISSN: | 1046-6673 |
| DOI: | 10.1681/asn.2015040385 |
| Popis: | The thrombotic microangiopathies (TMAs) and C3 glomerulopathies (C3Gs) include a spectrum of rare diseases such as atypical hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, C3GN, and dense deposit disease, which share phenotypic similarities and underlying genetic commonalities. Variants in several genes contribute to the pathogenesis of these diseases, and identification of these variants may inform the diagnosis and treatment of affected patients. We have developed and validated a comprehensive genetic panel that screens all exons of all genes implicated in TMA and C3G. The closely integrated pipeline implemented includes targeted genomic enrichment, massively parallel sequencing, bioinformatic analysis, and a multidisciplinary conference to analyze identified variants in the context of each patient’s specific phenotype. Herein, we present our 1-year experience with this panel, during which time we studied 193 patients. We identified 17 novel and 74 rare variants, which we classified as pathogenic (11), likely pathogenic (12), and of uncertain significance (68). Compared with controls, patients with C3G had a higher frequency of rare and novel variants in C3 convertase (C3 and CFB) and complement regulator (CFH, CFI, CFHR5, and CD46) genes (P |
| Databáze: | OpenAIRE |
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