دورية أكاديمية
A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome
| العنوان: | A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome |
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| المساهمون: | College of Medicine, Dept. of Pharmacology, Carolin E. Sadowski, Svjetlana Lovric, Shazia Ashraf, Werner L. Pabst, Heon Yung Gee, Stefan Kohl, Susanne Engelmann, Virginia Vega-Warner, Humphrey Fang, Jan Halbritter, Michael J. Somers, Weizhen Tan, Shirlee Shril, In챔s Fessi, Richard P. Lifton, Detlef Bockenhauer, Sherif El-Desoky, Jameela A. Kari, Martin Zenker, Markus J. Kemper, Dominik Mueller, Hanan M. Fathy, Neveen A. Soliman, Friedhelm Hildebrandt, Gee, Heon Yung |
| بيانات النشر: | American Society of Nephrology |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Adolescent, Adult, Age of Onset, Child, Preschool, Cohort Studies, Female, Genes, Wilms Tumor, Genetic Association Studies, Genetic Predisposition to Disease/epidemiology, Genotype, Heterozygote, Humans, Incidence, Infant, Intracellular Signaling Peptides and Proteins/genetics, Male, Membrane Proteins/genetics, Middle Aged, Mutation, Nephrotic Syndrome/congenital, Nephrotic Syndrome/epidemiology, Nephrotic Syndrome/genetics, Nephrotic Syndrome/physiopathology, Pedigree, Phenotype, Real-Time Polymerase Chain Reaction, Retrospective Studies, Risk Assessment |
| الوصف: | Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of ESRD in the first two decades of life. Effective treatment is lacking. First insights into disease mechanisms came from identification of single-gene causes of SRNS. However, the frequency of single-gene causation and its age distribution in large cohorts are unknown. We performed exon sequencing of NPHS2 and WT1 for 1783 unrelated, international families with SRNS. We then examined all patients by microfluidic multiplex PCR and next-generation sequencing for all 27 genes known to cause SRNS if mutated. We detected a single-gene cause in 29.5% (526 of 1783) of families with SRNS that manifested before 25 years of age. The fraction of families in whom a single-gene cause was identified inversely correlated with age of onset. Within clinically relevant age groups, the fraction of families with detection of the single-gene cause was as follows: onset in the first 3 months of life (69.4%), between 4 and 12 months old (49.7%), between 1 and 6 years old (25.3%), between 7 and 12 years old (17.8%), and between 13 and 18 years old (10.8%). For PLCE1, specific mutations correlated with age of onset. Notably, 1% of individuals carried mutations in genes that function within the coenzyme Q10 biosynthesis pathway, suggesting that SRNS may be treatable in these individuals. Our study results should facilitate molecular genetic diagnostics of SRNS, etiologic classification for therapeutic studies, generation of genotype-phenotype correlations, and the identification of individuals in whom a targeted treatment for SRNS may be available. ; restriction |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1046-6673 1533-3450 |
| العلاقة: | JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; J01779; OAK-2015-05412; https://ir.ymlib.yonsei.ac.kr/handle/22282913/156712Test; http://jasn.asnjournals.org/content/26/6/1279.abstractTest; T201504426; JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol.26(6) : 1279-1289, 2015 |
| DOI: | 10.1681/ASN.2014050489 |
| الإتاحة: | https://doi.org/10.1681/ASN.2014050489Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/156712Test http://jasn.asnjournals.org/content/26/6/1279.abstractTest |
| حقوق: | CC BY-NC-ND 2.0 KR ; https://creativecommons.org/licenses/by-nc-nd/2.0/krTest/ |
| رقم الانضمام: | edsbas.E744BB6C |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 10466673 15333450 |
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| DOI: | 10.1681/ASN.2014050489 |