Nephrotic Syndrome, Type 10

A number sign (#) is used with this entry because nephrotic syndrome type 10 (NPHS10) is caused by homozygous or compound heterozygous mutation in the EMP2 gene (602334) on chromosome 16p13.

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

Clinical Features

Gee et al. (2014) reported 4 patients from 3 unrelated families with childhood-onset nephrotic syndrome. Three of the patients were of Turkish descent, and 1 was African American. All had onset before age 3 years. Two Turkish sibs, who relapsed frequently with steroid treatment but had successful treatment with cyclophosphamide, were in remission without end-stage kidney disease in their twenties. Renal biopsy of the African American patient at age 5 years showed minimal change in disease, and electron microscopic analysis showed diffusely effaced foot processes of podocytes with microvillous changes.

Inheritance

The transmission pattern of NPHS10 in the families reported by Gee et al. (2014) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 4 patients from 3 unrelated families with nephrotic syndrome, Gee et al. (2014) identified homozygous or compound heterozygous mutations in the EMP2 gene (602334.0001-602334.0003). The mutations in the first family were found by a combination of homozygosity mapping and whole-exome sequencing of 67 families with the disorder. The mutations in the other 2 families were found by sequencing the EMP2 gene in over 1,600 individuals with nephrotic syndrome. Expression of the mutations failed to rescue the nephrotic syndrome phenotype of pericardial effusion in emp2-null zebrafish, consistent with a loss of function. The findings suggested that EMP2 is necessary for renal integrity. In vitro knockdown of EMP2 in human podocytes and endothelial cells resulted in an increased amount of caveolin-1 (CAV1; 601047) and decreased cell proliferation.