A 5-year-old nonconsanguineous girl of African American and Hispanic origin presented with nephrotic syndrome, including nephrotic-range proteinuria (UPC of > 29 mg/mg), edema, and hypoalbuminemia. Her initial serum creatinine was 654 μmol/L. Other pertinent laboratory evaluation at time of presentation included albumin of 19 g/L, BUN of 38 mmol/L, potassium of 6 mmol/L, bicarbonate of 12 mmol/L, calcium of 1.7 mmol/L, phosphorus of 2.5 mmol/L, and parathyroid hormone of 396 ng/L. She was oligoanuric and hemodialysis was initiated. An ultrasound of her kidneys showed diffuse echogenicity and loss of corticomedullary differentiation. Her history was significant for developmental delay and short stature. Her proteinuria presented in the setting of a previous respiratory illness but was not investigated. She has a normal-looking face and without dysmorphic features which was confirmed by the hospital’s geneticist. An ophthalmological examination did not show cataract or retinal changes. She has normal looking ears and exhibited normal hearing. She was normocephalic and did not have an exam consistent with GAMOS and no uro-genital anomalies were identified. She had normal birth history, and her family history was not significant for renal, cardiac or neurological development problems. In addition to her kidney involvement, she had developmental delays with autistic features; including delays in expressive language, fine motor, social communication and repetitive hand movements. She had expressive, receptive, and pragmatic language difficulties with a low score in the auditory comprehension subtest of the Preschool Language Scales. Additionally, while awaiting renal transplant, she had two episodes of heart failure requiring inotropic support after having adequate dialysis for more than a month. She had severely elevated B-type natriuretic peptide (BNP) levels (> 70,000 pg/mL) and her echocardiogram showed systolic and diastolic dysfunction (ejection fraction as low as 35%) and dilated cardiomyopathy features. After receiving aggressive nutritional support and blood pressure management, her cardiac function improved with ejection fractions range in 40–50%. She received a living related kidney transplant without recurrence of cardiac symptoms, and normal cardiac structures on echocardiograms with ejection fractions > 60%. Given that we know NUP93 does localize to cilia in Xenopus during cardiac development, we cannot exclude there may have been a contribution of the patient’s mutations to this phenotype. After her kidney transplant, she did not have recurrence of her nephrotic syndrome, but had a brief period of proteinuria (maximum UPC of 3.6) that was monitored closely and resolved within one week. Given her presentation of likely hereditary nephrotic syndrome, we sent clinical whole exome sequencing (WES). WES demonstrated a compound heterozygous mutations in NUP93; a maternal missense variant (chr16:56855426 A > G) c.A575G, p. Tyr192Cys and a paternal nonsense variant (chr16:56868107 C > G) c.C1605G, p. Tyr535Ter. Both variants are extremely rare, only 6 alleles of p.Tyr192Cys and 1 allele of p.Tyr535Ter have been reported previously in a large population database (gnomAD) with over 246,000 chromosomes, with a higher frequency of p.Tyr535Ter in African population (1 in 16,256). These allele frequencies are < 0.1%, which we have previously used as a cut off for filtering potentially pathogenic alleles []. The locations of the two variants are in the α helical domain of the NUP93 protein, as are some of the previously reported pathogenic mutations in Braun, et al. []. The tyrosine at position 192 is conserved through phylogeny, and the missense variant Tyr192Cys had high impact prediction scores for deleteriousness by CADD or SIFT. The nonsense variant p. Tyr535Ter likely results in defective protein structure either through truncation or nonsense-mediated mRNA decay. Additional analysis of her WES did not identify mutations related to cardiomyopathy.