Nephrotic Syndrome, Type 19

A number sign (#) is used with this entry because of evidence that nephrotic syndrome type 19 (NPHS19) is caused by compound heterozygous mutation in the NUP160 gene (607614) on chromosome 11p11. One such family has been reported.

For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).

Clinical Features

Braun et al. (2018) reported 2 Chinese sibs (family 17F00494) with nephrotic syndrome. The older sib presented at age 16 years with nephrotic syndrome that was resistant to therapy with steroids or other immunosuppressive drugs. Renal biopsy showed focal segmental glomerulosclerosis (FSGS). His renal function was impaired, resulting in stage 3 chronic kidney disease. His younger sister presented with proteinuria at age 7 years. Neither had extrarenal symptoms.

Inheritance

The transmission pattern of NPHS19 in the family reported by Braun et al. (2018) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 2 Chinese sibs (family 17F00494) with NPHS19, Braun et al. (2018) identified compound heterozygous mutations in the NUP160 gene (E803K, 607614.0001 and R910X, 607614.0002). The mutations, which were found by targeted exome sequencing of candidate genes and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed, but both were predicted to result in a loss of function. The patients were part of a large study in which various nucleopore (NUP) genes were found to be mutated in NPHS, suggesting a common pathogenic pathway.