Steroid-Resistant Nephrotic Syndrome Is Associated With a Unique Genetic Profile in a Highly Admixed Pediatric Population.

Introduction: The profile of genetic and nongenetic factors associated with progression to kidney failure (KF) in steroid-resistant nephrotic syndrome (SRNS) is largely unknown in admixed populations.

Methods: A total of 101 pediatric patients with primary SRNS were genetically assessed targeting Mendelian causes and status with a 62-NS-gene panel or whole exome sequencing, as well as genetic ancestry. Variant pathogenicity was evaluated using the American College Medical of Genetics and Genomics (ACMG) criteria.

Epigenomic and phenotypic characterization of DEGCAGS syndrome.

Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities syndrome (DEGCAGS, MIM #619488) is caused by biallelic, loss-of-function (LoF) ZNF699 variants, and is characterized by variable neurodevelopmental disability, discordant organ anomalies among full siblings and infant mortality. ZNF699 encodes a KRAB zinc finger protein of unknown function. We aimed to investigate the genotype-phenotype spectrum of DEGCAGS and the possibility of a diagnostic DNA methylation episignature, to facilitate the diagnosis of a highly variable condition lacking pathognomonic clinical findings.