Clinical and genetic characterization of children with cubilin variants,Pediatric Nephrology

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Clinical and genetic characterization of children with cubilin variants
Pediatric Nephrology ( IF 2.6 ) Pub Date : 2022-09-16 , DOI: 10.1007/s00467-022-05730-y
Neslihan Cicek ₁ , Harika Alpay ₁ , Sercin Guven ₁ , Ceren Alavanda ₂ , Özde Nisa Türkkan ₁ , Serim Pul ₁ , Ece Demirci ₁ , Nurdan Yıldız ₁ , Pınar Ata ₂ , Ibrahim Gokce ₁

Affiliation

Background

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.

Methods

Patients’ characteristics, serum creatinine, albumin, vitamin B₁₂ 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.

Results

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 B₁₂ 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.

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 prognosis. CUBN gene mutations may also present as FSGS which extends the spectrum of renal manifestation of these patients.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information

中文翻译：

具有 cubilin 变异的儿童的临床和遗传特征

背景

Cubilin 是负责近端小管重吸收白蛋白的受体蛋白之一，由CUBN基因编码。我们的目的是评估 6 名具有CUBN突变的蛋白尿患者的临床和遗传特征。

方法

患者特征、血清肌酐、白蛋白、维生素 B ₁₂水平、尿液分析、现货尿蛋白/肌酐、微量白蛋白/肌酐、β2 微球蛋白/肌酐比率、估计肾小球滤过率 (eGFR)、治疗、肾活检和遗传分析进行了评估。

结果

对偶然发现蛋白尿的 6 名患者（2 名女性，4 名男性）进行了评估。平均入院年龄和随访时间分别为 7.3 ± 2.9 和 6.5 ± 5.6 岁。血清白蛋白、肌酐和 eGFR 正常；尿液分析显示无血尿，C3、C4、ANA 和抗 DNA 均为阴性；所有患者的肾脏超声检查均正常。尿蛋白/肌酐为 0.9 ± 0.3 mg/mg，所有患者的微量白蛋白都很高。血清维生素B ₁₂两名患者低，四名正常。对 4 名患者进行了肾活检，其中 3 名在光镜下显示正常，1 名患有局灶节段性肾小球硬化 (FSGS)。基因测试显示 cubilin 的 C 末端部分有四个纯合突变和两个复合杂合突变。所有患者的 eGFR 均正常，并且在最后一次就诊时仍有非肾病范围的蛋白尿。