Ciliopathy variant burden and developmental delay in children with hypoplastic left heart syndrome

Genetics in Medicine

(2017)

19,

711–714

doi:10.1038/gim.2016.167

Received: 22 February 2016
Accepted: 31 August 2016
Published online: 27 October 2016

Abstract

Purpose:

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.

Methods:

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.

Results:

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.

Conclusion:

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.