|Title||Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Warejko, JK, Tan, W, Daga, A, Schapiro, D, Lawson, JA, Shril, S, Lovric, S, Ashraf, S, Rao, J, Hermle, T, Jobst-Schwan, T, Widmeier, E, Majmundar, AJ, Schneider, R, Gee, HYung, J Schmidt, M, Vivante, A, van der Ven, AT, Ityel, H, Chen, J, Sadowski, CE, Kohl, S, Pabst, WL, Nakayama, M, Somers, MJG, Rodig, NM, Daouk, G, Baum, M, Stein, DR, Ferguson, MA, Traum, AZ, Soliman, NA, Kari, JA, Desoky, SEl, Fathy, H, Zenker, M, Bakkaloglu, SA, Müller, D, Noyan, A, Ozaltin, F, Cadnapaphornchai, MA, Hashmi, S, Hopcian, J, Kopp, JB, Benador, N, Bockenhauer, D, Bogdanovic, R, Stajić, N, Chernin, G, Ettenger, R, Fehrenbach, H, Kemper, M, Munarriz, RLoza, Podracka, L, Büscher, R, Serdaroglu, E, Tasic, V, Mane, S, Lifton, RP, Braun, DA, Hildebrandt, F|
|Journal||Clin J Am Soc Nephrol|
|Date Published||2018 01 06|
BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome overwhelmingly progresses to ESRD. More than 30 monogenic genes have been identified to cause steroid-resistant nephrotic syndrome. We previously detected causative mutations using targeted panel sequencing in 30% of patients with steroid-resistant nephrotic syndrome. Panel sequencing has a number of limitations when compared with whole exome sequencing. We employed whole exome sequencing to detect monogenic causes of steroid-resistant nephrotic syndrome in an international cohort of 300 families.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Three hundred thirty-five individuals with steroid-resistant nephrotic syndrome from 300 families were recruited from April of 1998 to June of 2016. Age of onset was restricted to
RESULTS: In 74 of 300 families (25%), we identified a causative mutation in one of 20 genes known to cause steroid-resistant nephrotic syndrome. In 11 families (3.7%), we detected a mutation in a gene that causes a phenocopy of steroid-resistant nephrotic syndrome. This is consistent with our previously published identification of mutations using a panel approach. We detected a causative mutation in a known steroid-resistant nephrotic syndrome gene in 38% of consanguineous families and in 13% of nonconsanguineous families, and 48% of children with congenital nephrotic syndrome. A total of 68 different mutations were detected in 20 of 33 steroid-resistant nephrotic syndrome genes. Fifteen of these mutations were novel. , , , and were the most common genes in which we detected a mutation. In another 28% of families, we detected mutations in one or more candidate genes for steroid-resistant nephrotic syndrome.
CONCLUSIONS: Whole exome sequencing is a sensitive approach toward diagnosis of monogenic causes of steroid-resistant nephrotic syndrome. A molecular genetic diagnosis of steroid-resistant nephrotic syndrome may have important consequences for the management of treatment and kidney transplantation in steroid-resistant nephrotic syndrome.
|Alternate Journal||Clin J Am Soc Nephrol|
|PubMed Central ID||PMC5753307|
|Grant List||UM1 HG006504 / HG / NHGRI NIH HHS / United States |
UL1 TR001863 / TR / NCATS NIH HHS / United States
P30 DK079310 / DK / NIDDK NIH HHS / United States
S10 OD018521 / OD / NIH HHS / United States
R01 DK076683 / DK / NIDDK NIH HHS / United States
U54 HG006504 / HG / NHGRI NIH HHS / United States
T32 AR053461 / AR / NIAMS NIH HHS / United States
T32 DK007726 / DK / NIDDK NIH HHS / United States