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Analysis of 24 genes reveals a monogenic cause in 11.1% of cases with steroid-resistant nephrotic syndrome at a single center
- Source :
- Pediatric Nephrology. 33:305-314
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of end-stage renal disease (ESRD) among patients manifesting at under 25 years of age. We performed mutation analysis using a high-throughput PCR-based microfluidic technology in 24 single-gene causes of SRNS in a cohort of 72 families, who presented with SRNS before the age of 25 years. Within an 18-month interval, we obtained DNA samples, pedigree information, and clinical information from 77 consecutive children with SRNS from 72 different families seen at Boston Children’s Hospital (BCH). Mutation analysis was completed by combining high-throughput multiplex PCR with next-generation sequencing. We analyzed the sequences of 18 recessive and 6 dominant genes of SRNS in all 72 families for disease-causing variants. We identified the disease-causing mutation in 8 out of 72 (11.1%) families. Mutations were detected in the six genes: NPHS1 (2 out of 72), WT1 (2 out of 72), NPHS2, MYO1E, TRPC6, and INF2. Median age at onset was 4.1 years in patients without a mutation (range 0.5–18.8), and 3.2 years in those in whom the causative mutation was detected (range 0.1–14.3). Mutations in dominant genes presented with a median onset of 4.5 years (range 3.2–14.3). Mutations in recessive genes presented with a median onset of 0.5 years (range 0.1–3.2). Our molecular genetic diagnostic study identified underlying monogenic causes of steroid-resistant nephrotic syndrome in ~11% of patients with SRNS using a cost-effective technique. We delineated some of the therapeutic, diagnostic, and prognostic implications. Our study confirms that genetic testing is indicated in pediatric patients with SRNS.
- Subjects :
- Male
0301 basic medicine
Oncology
medicine.medical_specialty
Nephrotic Syndrome
Adolescent
Genotype
DNA Mutational Analysis
030232 urology & nephrology
Disease
Article
03 medical and health sciences
0302 clinical medicine
Internal medicine
Multiplex polymerase chain reaction
medicine
Humans
Genetic Predisposition to Disease
Child
Genetic testing
Genetics
medicine.diagnostic_test
business.industry
High-Throughput Nucleotide Sequencing
Infant
medicine.disease
Steroid-resistant nephrotic syndrome
INF2
030104 developmental biology
Nephrology
Child, Preschool
Pediatrics, Perinatology and Child Health
Mutation (genetic algorithm)
Mutation testing
Female
business
Nephrotic syndrome
Subjects
Details
- ISSN :
- 1432198X and 0931041X
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Pediatric Nephrology
- Accession number :
- edsair.doi.dedup.....132bb1b754f933aa2fbf9d353c773b5e