Clinical characteristics and genetic variation analysis of a child with nephrotic syndrome complicated with arrhythmia

Objective:To summarize and analyze the clinical characteristics and genetic variations of a child with steroid-resistant nephrotic syndrome (SRNS) complicated with arrhythmia (atrioventricular block and ventricular premature beats), so as to improve clinicians’understanding of the disease.Methods:The clinical data of a child with clinically confirmed SRNS, atrioventricular block, and ventricular premature beats were collected, and the relevant literature was reviewed to analyze the relationship between genetic variation and clinical characteristics.Results:The patient was a female, 8 years and 2 months old, with clinical manifestations of massive proteinuria, hypoproteinemia, hypercholesterolemia, glomerulogenic hematuria, and hypertension.The renal pathology showed focal segmental glomerulosclerosis (FSGS).Prednisone and tacrolimus were ineffective, which was consistent with the diagnosis of SRNS.At the same time, it was combined with arrhythmia such as atrioventricular block and ventricular premature beats.High-precision clinical exome detection revealed that there were compound heterozygous mutations c.412C> T (p.R138*) and c.8710T (p.R291W) in the Podocin coding gene(NPHS2) of the child; Sanger sequencing validation suggested that c.8710T (p.R291W) originated from the mother (heterozygous state), and c.412C> T (p.R138*) was a newly discovered mutation (heterozygous state).A heterozygous mutation c.4018G> A(p.V1340I) in the heart sodium channel pore-forming α subunit gene (SCN5A) was detected in the child, and Sanger sequencing showed that the mutation originated from the father (heterozygous state).Conclusion:The mutation in the NPHS2 gene is the cause of SRNS in this case, but nephrotic syndrome caused by this gene mutation usually has no extrarenal manifestations, and the occurrence of arrhythmia in the child may be associated with a heterozygous mutation in the SCN5A gene.