Dominant PAX2 mutations may cause steroid-resistant nephrotic syndrome and FSGS in children

Journal article


Publication Details

Author(s): Vivante A, Chacham OS, Shril S, Schreiber R, Mane SM, Pode-Shakked B, Soliman NA, Koneth I, Schiffer M, Anikster Y, Hildebrandt F
Journal: Pediatric Nephrology
Publication year: 2019
ISSN: 0931-041X


Abstract

BACKGROUND: Heterozygous PAX2 mutations cause renal coloboma syndrome (RCS) [OMIM no. 120330]. RCS is a renal syndromic disease encompassing retinal coloboma and sensorineural hearing loss. Recently, a causative role for PAX2 was reported in adult-onset nephrotic syndrome secondary to focal segmental glomerulosclerosis (FSGS). However, the prevalence of PAX2 mutations among large cohort of children with steroid-resistant nephrotic syndrome (SRNS) and FSGS has not been systematically studied.
METHODS: We employed whole-exome sequencing (WES) to identify the percentage of SRNS cases explained by monogenic mutations in known genes of SRNS/FSGS. As PAX2 mutations are not an established cause of childhood FSGS, we evaluated a cohort of 215 unrelated families with SRNS, in whom no underlying genetic etiology had been previously established.
RESULTS: Using WES, we identified 3 novel causative heterozygous PAX2 mutations in 3 out of the 215 unrelated index cases studied (1.3%). All three cases were detected in individuals from families with more than one affected and compatible with an autosomal dominant mode of inheritance (3/57 familial cases studied (5.2%)). The clinical diagnosis in three out of four pediatric index patients was done during routine medical evaluation.
CONCLUSIONS: Our findings demonstrate high frequency of PAX2 mutations in familial form of SRNS (5.2%) and further expand the phenotypic spectrum of PAX2 heterozygous mutations to include autosomal dominant childhood-onset FSGS. These results highlight the importance of including PAX2 in the list of genes known to cause FSGS in children.


FAU Authors / FAU Editors

Schiffer, Mario Prof. Dr. med.
Lehrstuhl für Innere Medizin IV


External institutions with authors

Boston Children's Hospital
Cairo University
Soroka Medical Center
Tel Aviv University


How to cite

APA:
Vivante, A., Chacham, O.S., Shril, S., Schreiber, R., Mane, S.M., Pode-Shakked, B.,... Hildebrandt, F. (2019). Dominant PAX2 mutations may cause steroid-resistant nephrotic syndrome and FSGS in children. Pediatric Nephrology. https://dx.doi.org/10.1007/s00467-019-04256-0

MLA:
Vivante, Asaf, et al. "Dominant PAX2 mutations may cause steroid-resistant nephrotic syndrome and FSGS in children." Pediatric Nephrology (2019).

BibTeX: 

Last updated on 2019-23-05 at 15:08