title: Ciliopathy variant burden and developmental delay in children with hypoplastic left heart syndrome.
abstract: To test the hypothesis that patients with hypoplastic left heart syndrome (HLHS) and developmental delay will have a higher average summative C-score in ciliopathy genes than patients with HLHS without developmental delay.
  
  
  
  Ciliopathy gene variant burden was determined utilizing a summative C-score for 14 ciliopathy genes in children with HLHS (n = 24). Mean summative C-scores were compared between children with and without developmental delay. Genome-wide randomizing gene sets were evaluated as a scoring control.
  
  
  
  Children with developmental delay had a mean summative C-score of 4.05 in ciliopathy genes as compared to a mean summative C-score of 2.02 for children without developmental delay. This difference in means was higher than 99.1% (empirical P value <0.01) of 2 million random lists of 14 genes.
  
  
  
  Genetically complex disorders such as ciliopathies can be assessed to determine phenotypic risk with summative C-score in appropriately chosen gene sets. If these results are replicated in subsequent cohorts, a diagnostic gene panel could identify risk for developmental delay and other ciliopathy-related comorbidities in infants with congenital heart disease.Genet Med advance online publication 27 October 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.167.
authors: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors: Gabrielle C
authors: GC
authors: Geddes
authors: Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors: Karl
authors: 0000-0002-7844-7326
authors: K
authors: Stamm
authors: Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors: Michael
authors: M
authors: Mitchell
authors: Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.
authors: Kathleen A
authors: KA
authors: Mussatto
authors: Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors: Aoy
authors: A
authors: Tomita-Mitchell