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Ciliopathy variant burden and developmental delay in children with hypoplastic left heart syndrome. Genet Med 2017 Jun;19(6):711-714

Date

10/28/2016

Pubmed ID

27787502

DOI

10.1038/gim.2016.167

Scopus ID

2-s2.0-85020225756 (requires institutional sign-in at Scopus site)   7 Citations

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.Genet Med advance online publication 27 October 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.167.

Author List

Geddes GC, Stamm K, Mitchell M, Mussatto KA, Tomita-Mitchell A

Authors

Aoy Tomita Mitchell PhD Professor in the Surgery department at Medical College of Wisconsin
Michael Edward Mitchell MD Chief, Professor in the Surgery department at Medical College of Wisconsin
Kathleen Mussatto Ph.D. Associate Professor in the School of Nursing department at Milwaukee School of Engineering