Exome sequencing for perinatal phenotypes: The significance of deep phenotyping

• DOI: 10.1002/pd.5616
• Publication Date: 2019-11-19T17:53:14Z
• Authors: Shagun Aggarwal; Venugopal Satidev...; Aneek Das Bhowmik; Ashwani Tandon; Aditya Kulkarni; Dhanya Lakshmi Na...; Amrita Bhattacherjee; Ashwin Dalal
• Keywords: Mendelian inheritance; Exome; Etiology; Human genetics

Abstract Objective To ascertain the performance of exome sequencing (ES) technology for determining etiological basis abnormal perinatal phenotypes and to study impact comprehensive phenotyping on variant prioritization. Methods A carefully selected cohort 32/204 fetuses with following postmortem/postnatal deep underwent ES identify a causative fetal phenotype. retrospective comparative analysis prenatal versus phenotype–based prioritization was performed aid Phenolyzer software. review literature reports done examine completeness phenotypic information cases in those how it impacted ES. Results In 18/32 (56%) fetuses, pathogenic/likely pathogenic identified. This included novel genotype‐phenotype associations, expanded known Mendelian disorders dual diagnoses. The revealed that putative diagnostic could not be identified findings alone 15/22 (68%) cases, indicating importance phenotype information. Literature supportive these but conclusive due marked heterogeneity involved studies. Conclusion Comprehensive is essential improving facilitating identification associations cohorts undergoing