ESPN 54th Annual Meeting

ESPN 2022


 
CLİNİCAL SPECTRUM OF CUBULIN MUTATIONS
NESLIHAN CICEK 1 HARIKA ALPAY 1 SERCIN GUVEN 1 OZDE NISA TURKKAN 1 SERIM POLAT 1 ECE DEMIRCI BODUR 1 CEREN ALAVANDA 2 NURDAN YILDIZ 1 PINAR ATA 2 IBRAHIM GOKCE 1

1- MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PEDIATRIC NEPHROLOGY
2- MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF GENETICS
 
Introduction:

 Cubulin is one of the receptor proteins responsible for the reabsorption of albumin in proximal tubule and is encoded by CUBN gene. We aimed to evaluate clinical and genetic characterization of five patients with proteinuria who had mutations in CUBN gene. 

Material and methods:

 Patients’ demographic charecteristics, serum creatinine, albumin, vitamin-B12 level, urine analysis, 24-hour urine protein, microalbumin, beta2 microglobulin, estimated glomerular filtration rates(eGFR), treatments, kidney biopsies and genetic analysis were evaluated.

Results:

 Five patients(1 female, 4 male) were evaluated with a mean admission age of 7.8±2.9 years and a follow up time of 7.7±5.6 years. All patients were referred to Pediatric Nephrology Department with an incidental finding of persistent protenuria. Serum albumine, creatinine, eGFR were in normal ranges, urine analysis revealed no hematuria at admission and at last visit and  C3, C4, ANA, anti-DNA were negative for all patients. 24-hour urine protein at admission was 18.1±4 mg/m2/hour and microalbumin was high in all patients. The maximum proteinuria during follow-up was 27.8±1.5 and 15.9±3.8 mg/m2/hour at last visit. Serum vitamin B12 was low in two patients and was normal in three patients. Renal ultrasonography was normal in all patients. Renal biopsy was performed in three patients, two demonstrated normal light microscopy, one focal segmental glomerulosclerosis(FSGS) and immunofluorescence examination was negative in three patients. Genetic tests revealed four homozygous and one compound-heterozygous mutation in C-terminal part of CUBN gene. All patients had normal eGFR and still non-nephrotic range proteinuria at last visit.

Conclusions:

 CUBN gene mutations should be considered in patients with isolated non-nephrotic range proteinuria and normal kidney function. Diagnosing these patients, who are thought to have a better prognosis, is important in terms of avoiding unnecessary treatment and predicting the prognosis. Besides CUBN gene mutations may also be presented as FSGS which extends the spectrum of renal manifestation of these patients.