Abstract
Nephrotic syndrome arising from monogenic mutations differs substantially from acquired ones in their clinical prognosis, progression, and disease management. Several pathogenic mutations in the COQ8B gene are known to cause nephrotic syndrome. Here, we used the whole-exome sequencing (WES) technology to decipher the genetic cause of nephrotic syndrome (CKD stage-V) in a large affected consanguineous family. Our study exposed a novel missense homozygous mutation NC_000019.9:g.41209497C > T; NM_024876.4:c.748G > A; NP_079152.3:p.(Asp250Asn) in the 9th exon of the COQ8B gene, co-segregated well with the disease phenotype. Our study provides the first insight into this homozygous condition, which has not been previously reported in 1000Genome, ClinVar, ExAC, and genomAD databases. In addition to the pathogenic COQ8B variant, the WES data also revealed some novel and recurrent mutations in the GLA, NUP107, COQ2, COQ6, COQ7 and COQ9 genes. The novel variants observed in this study have been submitted to the ClinVar database and are publicly available online with the accessions: SCV001451361.1, SCV001451725.1 and SCV001451724.1. Based on the patient's clinical history and genomic data with in silico validation, we conclude that pathogenic mutation in the COQ8B gene was causing kidney failure in an autosomal recessive manner. We recommend WES technology for genetic testing in such a consanguineous family to not only prevent the future generation, but early detection can help in disease management and therapeutic interventions.
Highlights
Nephrotic syndrome arising from monogenic mutations differs substantially from acquired ones in their clinical prognosis, progression, and disease management
Massive parallel sequencing (MPS) or next-generation sequencing (NGS) technologies help us conveniently to unravel the genetic basis of the disease, which could be used as a primary diagnostic tool for medical genetic testing
We employed the whole-exome sequencing (WES) approach to precisely identify the functional pathogenic mutations in a large consanguineous family affected with nephrotic syndrome (CKD stage-V or ESRD)
Summary
Nephrotic syndrome arising from monogenic mutations differs substantially from acquired ones in their clinical prognosis, progression, and disease management. Several pathogenic mutations in the COQ8B gene are known to cause nephrotic syndrome. We used the whole-exome sequencing (WES) technology to decipher the genetic cause of nephrotic syndrome (CKD stage-V) in a large affected consanguineous family. Based on the patient’s clinical history and genomic data with in silico validation, we conclude that pathogenic mutation in the COQ8B gene was causing kidney failure in an autosomal recessive manner. Pathogenic mutations in any of the genes encoding enzymes of the CoQ10 biosynthetic pathway have been associated with nephrotic syndrome or C KD7–10. We employed the whole-exome sequencing (WES) approach to precisely identify the functional pathogenic mutations in a large consanguineous family affected with nephrotic syndrome (CKD stage-V or ESRD)
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