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Rationale: Congenital nephrotic syndrome (CNS) is a heterogeneous disorder in which massive proteinuria, hypoproteinemia, and hyperlipidemia and marked edema are the main manifestations before 3 months-of-age. Here, we present a case involving the genetic diagnosis of a child with CNS.Patient concerns: A 31-day-old male infant with diarrhea for 25 days and generalized edema for more than 10 days. There was no family history of kidney disease. On proband whole exome sequencing, a compound heterozygous mutation of the NPHS1 gene was identified, including a novel in-frame mutation in exon 14 (c.1864_1866dupACC p. T622dup) and a missense mutation in exon 8 (c.928G>A p. D310N).Diagnoses: Based on the clinical and genetic findings, this patient was finally diagnosed with CNS. Interventions:The main treatment options for the patient were 2-fold: anti-infective treatment and symptomatic treatment.Outcomes: The patient died in follow-up 2 months later; the specific reason for death was unclear.Lessons: Whole exome sequencing and Sanger sequencing confirmed that the infant had CNS. Our study identified a novel mutation in an infant, thus expanding the gene-mutation spectrum of the NPHS1 gene, thus providing an efficient prenatal screening strategy and early genetic counseling.Abbreviations: AFP = alpha-fetoprotein, CNF = CNS of the Finnish type, CNS = congenital nephrotic syndrome, WES = whole exome sequencing.

Background Intellectual disability (ID) represents a neurodevelopmental disorder, which is characterized by marked defects in the intellectual function and adaptive behavior, with an onset during the developmental period. ID is mainly caused by genetic factors, and it is extremely genetically heterogeneous. This study aims to identify the genetic cause of ID using trio‐WES analysis. Methods We recruited four pediatric patients with unexplained ID from non‐consanguineous families, who presented at the Department of Pediatrics, Guizhou Provincial People's Hospital. Whole‐exome sequencing (WES) and Sanger sequencing validation were performed in the patients and their unaffected parents. Furthermore, conservative analysis and protein structural and functional prediction were performed on the identified pathogenic variants. Results We identified five novel de novo mutations from four known ID‐causing genes in the four included patients, namely COL4A1 (c.2786T>A, p.V929D and c.2797G>A, p.G933S), TBR1 (c.1639_1640insCCCGCAGTCC, p.Y553Sfs*124), CHD7 (c.7013A>T, p.Q2338L), and TUBA1A (c.1350del, p.E450Dfs*34). These mutations were all predicted to be deleterious and were located at highly conserved domains that might affect the structure and function of these proteins. Conclusion Our findings contribute to expanding the mutational spectrum of ID‐related genes and help to deepen the understanding of the genetic causes and heterogeneity of ID.