@article {651, title = {Dominant PAX2 mutations may cause steroid-resistant nephrotic syndrome and FSGS in children.}, journal = {Pediatr Nephrol}, volume = {34}, year = {2019}, month = {2019 Sep}, pages = {1607-1613}, 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.

}, issn = {1432-198X}, doi = {10.1007/s00467-019-04256-0}, author = {Vivante, Asaf and Chacham, Orna Staretz and Shril, Shirlee and Schreiber, Ruth and Mane, Shrikant M and Pode-Shakked, Ben and Soliman, Neveen A and Koneth, Irene and Schiffer, Mario and Anikster, Yair and Hildebrandt, Friedhelm} }