<![CDATA[Expanding the spectrum of novel candidate genes using trio exome sequencing and identification of monogenic cause in 27.5% of 320 families with steroid-resistant nephrotic syndrome]]>

1 JournalArticle zh-CHS <![CDATA[Expanding the spectrum of novel candidate genes using trio exome sequencing and identification of monogenic cause in 27.5% of 320 families with steroid-resistant nephrotic syndrome]]> Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of pediatric end-stage renal disease. Monogenic causes have been detected in 11%–45% of pediatric SRNS using exome sequencing,1, 2, 3 leaving a large proportion of cases without a molecular diagnosis. Here, we report employing trio exome sequencing analysis to detect established and novel causes of SRNS in an international cohort of 320 unrelated families with pediatric SRNS. In 88/320 families (27.5%), exome sequencing revealed a pathogenic variant in a known monogenic SRNS gene. In 18 families (5.6%), we detected a causative variant in a phenocopy gene. In families without a molecular diagnosis, exome sequencing data was evaluated for variants in novel genes. In 18.1% (58/320) of families, we detected variants in a single novel candidate gene for SRNS. In non-consanguineous families, trio analysis increased the rate of novel candidate gene discovery from 15.9% in singlets to 28.8% in duos/trios by detection of deleterious compound heterozygous and de novo rare variants (Fig. 1).

]]>