Department of Pediatric Nephrology, Marmara University School of Medicine, Fevzi Çakmak Mahallesi Muhsin Yazıcıoğlu Caddesi No: 10, Ust Kaynarca/Pendik, Istanbul, Turkey.
Department of Medical Genetics, Marmara University School of Medicine, Fevzi Çakmak Mahallesi Muhsin Yazıcıoğlu Caddesi No: 10, Ust Kaynarca/Pendik, Istanbul, Turkey.
Pediatr Nephrol. 2023 Apr;38(4):1381-1385. doi: 10.1007/s00467-022-05730-y. Epub 2022 Sep 16.
Cubilin is one of the receptor proteins responsible for reabsorption of albumin in proximal tubules and is encoded by the CUBN gene. We aimed to evaluate clinical and genetic characterization of six patients with proteinuria who had CUBN mutations.
Patients' characteristics, serum creatinine, albumin, vitamin B levels, urine analysis, spot urine protein/creatinine, microalbumin/creatinine, beta-2 microglobulin/creatinine ratios, estimated glomerular filtration rates (eGFR), treatments, kidney biopsies, and genetic analyses were evaluated.
Six patients (2 female, 4 male) with an incidental finding of proteinuria were evaluated. Mean admission age and follow-up time were 7.3 ± 2.9 and 6.5 ± 5.6 years, respectively. Serum albumin, creatinine, and eGFR were normal; urine analysis revealed no hematuria, and C3, C4, ANA, and anti-DNA were negative; kidney ultrasonography was normal for all patients. Urine protein/creatinine was 0.9 ± 0.3 mg/mg, and microalbumin was high in all patients. Serum vitamin B was low in two patients and normal in four. Kidney biopsy was performed in four patients, three demonstrated normal light microscopy, and there was one focal segmental glomerulosclerosis (FSGS). Genetic tests revealed four homozygous and two compound heterozygous mutations in the C-terminal part of cubilin. All patients had normal eGFR and still had non-nephrotic range proteinuria at last visit.
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 prognosis. CUBN gene mutations may also present as FSGS which extends the spectrum of renal manifestation of these patients. A higher resolution version of the Graphical abstract is available as Supplementary information.
穹窿蛋白是负责重吸收近端小管内白蛋白的受体蛋白之一，由 CUBN 基因编码。我们旨在评估 6 例具有 CUBN 突变的蛋白尿患者的临床和遗传特征。
评估了患者的特征、血清肌酐、白蛋白、维生素 B 水平、尿液分析、随机尿蛋白/肌酐、微量白蛋白/肌酐、β-2 微球蛋白/肌酐比值、估算肾小球滤过率（eGFR）、治疗、肾活检和基因分析。
评估了 6 例（2 例女性，4 例男性）偶然发现蛋白尿的患者。入院时的平均年龄和随访时间分别为 7.3±2.9 岁和 6.5±5.6 岁。血清白蛋白、肌酐和 eGFR 正常；尿液分析未见血尿，C3、C4、ANA 和抗-DNA 均为阴性；所有患者的肾脏超声均正常。尿蛋白/肌酐为 0.9±0.3mg/mg，所有患者的微量白蛋白均升高。2 例患者血清维生素 B 水平低，4 例患者血清维生素 B 水平正常。4 例患者进行了肾活检，3 例光镜正常，1 例局灶节段性肾小球硬化（FSGS）。基因检测显示穹窿蛋白基因的 C 末端有 4 个纯合子和 2 个复合杂合突变。所有患者的 eGFR 均正常，最后一次就诊时仍有非肾病范围的蛋白尿。
对于孤立性非肾病范围蛋白尿和正常肾功能的患者，应考虑 CUBN 基因突变。诊断这些被认为预后较好的患者对于避免不必要的治疗和预测预后很重要。穹窿蛋白基因突变也可能表现为 FSGS，这扩展了这些患者肾脏表现谱。可在补充资料中查看更高分辨率的图文摘要。
