Clinical Utility of Proband Only Clinical Exome Sequencing in Neurodevelopmental Disorders

Karthika Ajit Valaparambil; Alfiya Fasaludeen; Lakshmi Priya; Ramshekhar N Menon; Ramesh Menon; Soumya Sundaram

doi:10.1007/s12098-023-04916-y

Clinical Utility of Proband Only Clinical Exome Sequencing in Neurodevelopmental Disorders

Indian J Pediatr. 2023 Nov 9. doi: 10.1007/s12098-023-04916-y. Online ahead of print.

Authors

Karthika Ajit Valaparambil¹, Alfiya Fasaludeen¹, Lakshmi Priya¹, Ramshekhar N Menon², Ramesh Menon³, Soumya Sundaram⁴

Affiliations

¹ Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, Kerala, India.
² Pediatric Neurology and Neurodevelopmental Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, Kerala, India.
³ Department of Bioinformatics, MedGenome Labs, Bangalore, India.
⁴ Pediatric Neurology and Neurodevelopmental Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, Kerala, India. ssdr.soumya@gmail.com.

PMID: 37943464
DOI: 10.1007/s12098-023-04916-y

Abstract

Chromosomal microarray is recommended as the first line of investigation in neurodevelopmental disorders (NDDs). However, advances in next-generation sequencing have unraveled more than 900 genes associated with NDDs, thus improving the genetic diagnosis. Therefore, this study was conducted to explore the utility of clinical exome sequencing (CES) in NDDs from a tertiary care centre in India. A retrospective observational analysis of 78 children with NDDs for whom CES was performed between 2017 and 2021 was conducted. The American College of Medical Genetics and Genomics (ACMG) criteria were used to classify the variants. The mean age was 5.8 ± 3.6 y, and 42 (53%) were male. Pathogenic, likely pathogenic, and variants of uncertain significance (VUS) were observed in 22 (28.2%), 10 (12.8%), and 26 (33.3%) patients, respectively, which included five copy number variants. The diagnostic yield for pathogenic and likely pathogenic variants in NDDs by CES was 41%, which was reasonably high.

Keywords: Autism spectrum disorder; Clinical exome sequencing; Diagnostic yield; Intellectual disability; Neurodevelopmental disorders; Next generation sequencing.