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

Vivante A, Chacham OS, Shril S, Schreiber R, Mane SM, Pode-Shakked B, Soliman NA, Koneth I, Schiffer M, Anikster Y, Hildebrandt F (2019)

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Publication Type: Journal article

Publication year: 2019

Journal

DOI: 10.1007/s00467-019-04256-0

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.

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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).

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