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Several pathogenic mutations in the <jats:italic>COQ8B<\/jats:italic> 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\u2009&gt;\u2009T; NM_024876.4:c.748G\u2009&gt;\u2009A; NP_079152.3:p.(Asp250Asn) in the 9th exon of the <jats:italic>COQ8B<\/jats:italic> 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 <jats:italic>COQ8B<\/jats:italic> variant, the WES data also revealed some novel and recurrent mutations in the <jats:italic>GLA, NUP107, COQ2, COQ6, COQ7<\/jats:italic> and <jats:italic>COQ9<\/jats:italic> 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 <jats:italic>COQ8B<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/s41598-021-92023-3","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T10:03:07Z","timestamp":1624615387000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Whole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome"],"prefix":"10.1038","volume":"11","author":[{"given":"Mohd","family":"Fareed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikas","family":"Makkar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi","family":"Angral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Afzal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gurdarshan","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"92023_CR1","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1001\/jama.2017.4046","volume":"317","author":"AK Bello","year":"2017","unstructured":"Bello, A. 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