Dataset Information

Steroid-resistant nephrotic syndrome in infants caused by a novel compound heterozygous mutation of the NUP93: A CARE case report.

ABSTRACT:

Rationale

Steroid-resistant nephrotic syndrome (SRNS) is a special kidney disease. SRNS is characterized by steroid-resistant, clinical variability, and genetic heterogeneity. Patients with SRNS often may eventually need renal transplantation.

Patient concerns

A 10-month-old Chinese male infant presented with oliguria, renal dysfunction, hypertension, and anemia.

Diagnoses

Combined with clinical manifestations, laboratory testing and sequencing results, the patient was diagnosed as SRNS.

Interventions

Combined intravenous methylprednisolone and cefoperazone sulbactam did not improve the patient's condition. Thus, SRNS associated with hereditary nephrotic syndrome was strongly suspected. Genetic testing for hereditary renal disease of the patient revealed 2 novel heterozygous mutations in the Nucleoporin 93 (NUP93) gene, which were predicted pathogenic and harmful by bioinformatic softwares of SIFT, PolyPhen_2 and REVEL.

Outcomes

As general physical health deterioration and renal dysfunction, the patient died of a severe infection.

Lessons

The novel NUP93 heterozygous mutations identified in the current study broadened the genetic spectrum of SRNS and further deepened our insight into pathogenic mutations of NUP93 to improve disease diagnosis.

SUBMITTER: Zhao B

PROVIDER: S-EPMC7886470 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Steroid-resistant nephrotic syndrome in infants caused by a novel compound heterozygous mutation of the NUP93: A CARE case report.

Zhao Bo B Chen Ji-Yu JY Liao Ya-Bin YB Li Yan-Fang YF Jiang Xue-Mei XM Bi Xin X Yang Mi-Feng MF Li Li L Cui Jing-Jing JJ

Medicine 20210201 6

<h4>Rationale</h4>Steroid-resistant nephrotic syndrome (SRNS) is a special kidney disease. SRNS is characterized by steroid-resistant, clinical variability, and genetic heterogeneity. Patients with SRNS often may eventually need renal transplantation.<h4>Patient concerns</h4>A 10-month-old Chinese male infant presented with oliguria, renal dysfunction, hypertension, and anemia.<h4>Diagnoses</h4>Combined with clinical manifestations, laboratory testing and sequencing results, the patient was diag ...[more]

PMID: 33578576

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Project description:Genetic testing in nephrotic syndrome may identify heterozygous predicted-pathogenic variants (HPPVs) in autosomal recessive (AR) genes that are known to cause disease in the homozygous or compound heterozygous state. In such cases, it can be difficult to define the variant's true significance and questions remain about whether a second pathogenic variant has been missed during analysis or whether the variant is an incidental finding. There are now known to be over 70 genes associated with nephrotic syndrome, the majority inherited as an AR trait. Knowledge of whether such HPPVs occur with equal frequency in patients compared to the general population would assist interpretation of their significance. Exome sequencing was performed on 187 Steroid-Resistant Nephrotic Syndrome (SRNS) paediatric patients recruited to a UK rare disease registry plus originating from clinics at Evelina, London. 59 AR podocytopathy linked genes were analysed in each patient and a list of HPPVs created. We compared the frequency of detected HPPVs with a 'control' population from the gnomAD database containing exome data from approximately 50,000 individuals. A bespoke filtering process was used for both patients and controls to predict 'likely pathogenicity' of variants. In total 130 Caucasian SRNS patients were screened across 59 AR genes and 201 rare heterozygous variants were identified. 17/201 (8.5%) were assigned as 'likely pathogenic' (HPPV) using our bespoke filtering method. Comparing each gene in turn, for SRNS patients with a confirmed genetic diagnosis, in 57 of the 59 genes we found no statistically significant difference in the frequency of these HPPVs between patients and controls (In genes ARHGDIA and TP53RK, we identified a significantly higher number of HPPVs in the control population compared with the patients when filtering was performed with 'high stringency' settings only). In the SRNS patients without a genetics diagnosis confirmed, there was no statistically significant difference identified in any gene between patient and control. In children with SRNS, we propose that identification of HPPV in AR podocytopathy linked genes is not necessarily representative of pathogenicity, given that the frequency is similar to that seen in controls for the majority. Whilst this may not exclude the presence of genetic kidney disease, this type of heterozygous variant is unlikely to be causal and each result must be interpreted in its clinical context.

Dataset Information

Steroid-resistant nephrotic syndrome in infants caused by a novel compound heterozygous mutation of the NUP93: A CARE case report.

Rationale

Patient concerns

Diagnoses

Interventions

Outcomes

Lessons

Publications

Steroid-resistant nephrotic syndrome in infants caused by a novel compound heterozygous mutation of the NUP93: A CARE case report.

Similar Datasets

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