title: Genomic imbalances in pediatric patients with chronic kidney disease.
abstract: BACKGROUND
  There is frequent uncertainty in the identification of specific etiologies of chronic kidney disease (CKD) in children. Recent studies indicate that chromosomal microarrays can identify rare genomic imbalances that can clarify the etiology of neurodevelopmental and cardiac disorders in children; however, the contribution of unsuspected genomic imbalance to the incidence of pediatric CKD is unknown.
  
  
  METHODS
  We performed chromosomal microarrays to detect genomic imbalances in children enrolled in the Chronic Kidney Disease in Children (CKiD) prospective cohort study, a longitudinal prospective multiethnic observational study of North American children with mild to moderate CKD. Patients with clinically detectable syndromic disease were excluded from evaluation. We compared 419 unrelated children enrolled in CKiD to multiethnic cohorts of 21,575 children and adults that had undergone microarray genotyping for studies unrelated to CKD.
  
  
  RESULTS
  We identified diagnostic copy number disorders in 31 children with CKD (7.4% of the cohort). We detected 10 known pathogenic genomic disorders, including the 17q12 deletion HNF1 homeobox B (HNF1B) and triple X syndromes in 19 of 419 unrelated CKiD cases as compared with 98 of 21,575 control individuals (OR 10.8, P = 6.1 × 10⁻²⁰). In an additional 12 CKiD cases, we identified 12 likely pathogenic genomic imbalances that would be considered reportable in a clinical setting. These genomic imbalances were evenly distributed among patients diagnosed with congenital and noncongenital forms of CKD. In the vast majority of these cases, the genomic lesion was unsuspected based on the clinical assessment and either reclassified the disease or provided information that might have triggered additional clinical care, such as evaluation for metabolic or neuropsychiatric disease.
  
  
  CONCLUSIONS
  A substantial proportion of children with CKD have an unsuspected genomic imbalance, suggesting genomic disorders as a risk factor for common forms of pediatric nephropathy. Detection of pathogenic imbalances has practical implications for personalized diagnosis and health monitoring in this population.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00327860.
  
  
  BACKGROUND
  This work was supported by the NIH, the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute.
authors.forename: Miguel
authors.initials: M
authors.lastname: Verbitsky
authors.forename: Simone
authors.initials: S
authors.lastname: Sanna-Cherchi
authors.forename: David A
authors.initials: DA
authors.lastname: Fasel
authors.forename: Brynn
authors.initials: B
authors.lastname: Levy
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kiryluk
authors.forename: Matthias
authors.initials: M
authors.lastname: Wuttke
authors.forename: Alison G
authors.initials: AG
authors.lastname: Abraham
authors.forename: Frederick
authors.initials: F
authors.lastname: Kaskel
authors.forename: Anna
authors.initials: A
authors.lastname: Köttgen
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Warady
authors.forename: Susan L
authors.initials: SL
authors.lastname: Furth
authors.forename: Craig S
authors.initials: CS
authors.lastname: Wong
authors.forename: Ali G
authors.initials: AG
authors.lastname: Gharavi
mesh_terms: D000293:Adolescent; D015984:Causality; D002648:Child; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000453:epidemiology / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D046228:Microarray Analysis; D015995:Prevalence; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000235:genetics*; D017384:Sequence Deletion; D014481:United States / Q000453:epidemiology