Phenotypic characterization of a pediatric cohort with cystinuria and usefulness of newborn screening.

Background: Cystinuria is an inherited metabolic disease involving the defective transport of cystine and the dibasic amino acids in the renal proximal tubules that causes the formation of stones in the urinary system. In our regional child health program, cystinuria is included in newborn metabolic screening. Our objectives are the phenotypic characterization of our cystinuric pediatric cohort and to present our experience in neonatal cystinuria screening.

Clinical and genetic characterization of a cohort of proteinuric patients with biallelic CUBN variants.

Background: Proteinuria is a well-known risk factor for progressive kidney impairment. Recently, C-terminal cubilin (CUBN) variants have been associated with isolated proteinuria without progression of kidney disease.

Methods: Genetic testing of 347 families with proteinuria of suspected monogenic cause was performed by next-generation sequencing of a custom-designed kidney disease gene panel.

Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players.

Background: Inherited kidney diseases are one of the leading causes of chronic kidney disease (CKD) that manifests before the age of 30 years. Precise clinical diagnosis of early-onset CKD is complicated due to the high phenotypic overlap, but genetic testing is a powerful diagnostic tool. We aimed to develop a genetic testing strategy to maximize the diagnostic yield for patients presenting with early-onset CKD and to determine the prevalence of the main causative genes.

A kidney-disease gene panel allows a comprehensive genetic diagnosis of cystic and glomerular inherited kidney diseases.

Molecular diagnosis of inherited kidney diseases remains a challenge due to their expanding phenotypic spectra as well as the constantly growing list of disease-causing genes. Here we develop a comprehensive approach for genetic diagnosis of inherited cystic and glomerular nephropathies. Targeted next generation sequencing of 140 genes causative of or associated with cystic or glomerular nephropathies was performed in 421 patients, a validation cohort of 116 patients with previously known mutations, and a diagnostic cohort of 207 patients with suspected inherited cystic disease and 98 patients with glomerular disease.

Contribution of the TTC21B gene to glomerular and cystic kidney diseases.

Background: The TTC21B gene was initially described as causative of nephronophthisis (NPHP). Recently, the homozygous TTC21B p.P209L mutation has been identified in families with focal segmental glomerulosclerosis (FSGS) and tubulointerstitial lesions.