ESPN 51th Annual Meeting

ESPN 2018


 
TARGETED NEXT GENERATION SEQUENCING IN CHIDREN WITH INFANTILE NEPHROTIC SYNDROME
LARISA PRIKHODINA 1 LARISA PRIKHODINA 2 EKATERINA STOLYAREVICH 3 PETER SHATALOV 1

1- RESEARCH & CLINICAL INSTITUTE FOR PEDIATRICS, PIROGOV RUSSIAN NATIONAL RESEARCH MEDICAL UNIVERSITY, Moscow, Russia
2- RUSSIAN ACADEMY OF MEDICAL CONTINUOUS POSTGRADUATE EDUCATION, Moscow, Russia
3- MOSCOW CITY CLINICAL HOSPITAL № 52, Moscow, Russia
 
Introduction:

Infantile nephrotic syndrome (NS) is a rare, genetically heterogeneous group of glomerulopathies with the onset of the disease at the age of 4-12 months. We aimed to determine the causative gene mutations in children with infantile NS through next generation sequencing (NGS).

Material and methods:

The mutational analysis was performed in 8 children (4M/4F) aged 3.2 (IQR: 3.0; 6.1) years with infantile NS from nonconsanguineous families. Renal biopsy revealed FSGS in 7/8 (87.5%) the affected children. Targeted NGS covering 68 genes associated with steroid-resistant NS (SRNS) with confirmation by direct Sanger sequencing were applied.

Results:

A total of 13 different mutations were detected in 9/68 (13.2%) genes associated with SRNS in 7/8 (87.5%) children with infantile NS. 3/13 (23.1%) of these mutations were novel. Monogenic cause of infantile NS was identified in 4/8 (50%) children. We determined homozygous mutations in NPHS2 gene (n=2), compound-heterozygous mutations in NPHS1 and ITGB4 genes (n=1), heterozygous mutations in WT1 gene (n=1). Digenic inheritance had 2 patients: PTPRO with SCARB2 (n=1) and WT1 with ITGB4 (n=1). Extrarenal syndromic features were presented in 3 of the affected children: Wilms tumor (n=2), microcephaly with deafness (n=1). 2 patients with homozygous NPHS2 mutations progressed to ESKD by the age of 6 years. Kidney transplantation was performed in one of them without disease recurrence after transplantation for 14 months.

Conclusions:

We conclude that monogenic cause of infantile NS was identified in 50% of children with the most prevalent mutations in NPHS2, NPHS1, ITGB4 and WT1 genes. A molecular genetic diagnosis of infantile NS through NGS may have important consequences for the clinical management of patients and prediction of a risk for disease recurrence after kidney transplantation.