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

Asaf Vivante, Orna Staretz Chacham, Shirlee Shril, Ruth Schreiber, Shrikant M. Mane, Ben Pode-Shakked, Neveen A. Soliman, Irene Koneth, Mario Schiffer, Yair Anikster, Friedhelm Hildebrandt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1607-1613
Number of pages7
JournalPediatric Nephrology
Issue number9
StatePublished - 1 Sep 2019


FundersFunder number
Broad and Yale Centers for Mendelian Genomics
National Institutes of HealthR01-DK076683, HLR
National Human Genome Research InstituteU54 HG006504, UM1 HG008900
NIH Office of the DirectorS10OD018521
Boston Children's Hospital
Bundesministerium für Bildung und ForschungSTOP-FSGS 01GM1518A


    • Congenital anomalies of the kidneys and urinary tract (CAKUT)
    • FSGS
    • SRNS and PAX2


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