Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Warejko Jillian K, Tan Weizhen, Daga Ankana, Schapiro David, Lawson Jennifer A, Shril Shirlee, Lovric Svjetlana, Ashraf Shazia, Rao Jia, Hermle Tobias, Jobst-Schwan Tilman, Widmeier Eugen, Majmundar Amar J, Schneider Ronen, Gee Heon Yung, Schmidt J Magdalena, Vivante Asaf, van der Ven Amelie T, Ityel Hadas, Chen Jing, Sadowski Carolin E, Kohl Stefan, Pabst Werner L, Nakayama Makiko, Somers Michael J G, Rodig Nancy M, Daouk Ghaleb, Baum Michelle, Stein Deborah R, Ferguson Michael A, Traum Avram Z, Soliman Neveen A, Kari Jameela A, El Desoky Sherif, Fathy Hanan, Zenker Martin, Bakkaloglu Sevcan A, Müller Dominik, Noyan Aytul, Ozaltin Fatih, Cadnapaphornchai Melissa A, Hashmi Seema, Hopcian Jeffrey, Kopp Jeffrey B, Benador Nadine, Bockenhauer Detlef, Bogdanovic Radovan, Stajić Nataša, Chernin Gil, Ettenger Robert, Fehrenbach Henry, Kemper Markus, Munarriz Reyner Loza, Podracka Ludmila, Büscher Rainer, Serdaroglu Erkin, Tasic Velibor, Mane Shrikant, Lifton Richard P, Braun Daniela A, Hildebrandt Friedhelm
Аннотация
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 <25 years of age. Exome data were evaluated for 33 known monogenic steroid-resistant nephrotic syndrome genes.
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. NPHS1, PLCE1, NPHS2, and SMARCAL1 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.