Exploring the clinical utility of exome sequencing/Mono, Duo, Trio in prenatal testing: a retrospective study in a tertiary care centre in South India

Hemalatha Ilangovan; Janane Elangovan; Sumita Danda; Manisha M. Beck; Preethi Navaneethan; Rekha Athiyarath

doi:10.1515/jpm-2023-0485

Article

Exploring the clinical utility of exome sequencing/Mono, Duo, Trio in prenatal testing: a retrospective study in a tertiary care centre in South India

Hemalatha Ilangovan , Janane Elangovan , Sumita Danda , Manisha M. Beck , Preethi Navaneethan and Rekha Athiyarath

Published/Copyright: May 7, 2024

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From the journal Journal of Perinatal Medicine Volume 52 Issue 5

Abstract

Objectives

With the availability of Next Generation Sequencing (NGS) diagnosis of genetic disorders has improved significantly. Its use is also applicable to ascertain diagnosis and management in a perinatal setting. The study aims to detect the genetic aetiology of various congenital structural and functional defects using NGS technology in the reproductive cohort at a tertiary centre. The secondary objective is to address challenges in the interpretation of variants.

Methods

This was a retrospective study of couples who underwent exome sequencing (Mono-testing proband only or Duo-testing parents only or Trio-testing proband and parents) for suspected single gene disorders between years 2020–2022 at a tertiary care perinatal center in the South India. American College of Medical Genetics (ACMG) guidelines were followed to classify the pathogenicity of the variants identified by exome sequencing.

Results

The overall diagnostic yield as defined by pathogenic/likely pathogenic variants obtained was (23/43) 53.4 %. The individual subsets have the following diagnostic yield viz., Mono 5/6 (83 %); Carrier 16/32 (50 %); Trio 2/5 (40 %). Diagnostic yield was significantly higher in consanguineous couples. However, miscarriage history, and organ system involvement did not have a significant effect on the diagnostic yield. Prenatal diagnosis was offered for seven patients based on the exome result. One fetus was confirmed with a compound heterozygous pathogenic variant.

Conclusions

Diagnostic yield of exome sequencing in our cohort was 53 %. The detection of pathogenic variants was maximum in those cases undergoing Mono exome sequencing. In places where there is a high prevalence of consanguinity and endogamy, NGS may be offered as first line test in the context of prenatal diagnosis.

Keywords: syndrome; genetic counselling; consanguinity; congenital; proband

Corresponding author: Sumita Danda, Department of Clinical Genetics, Christian Medical College, Vellore 632004, Tamil Nadu, India, E-mail: sumita_danda@hotmail.com

Hemalatha Ilangovan and Janane Elangovan contributed equally to this work

Acknowledgments

We thank Paramasivam, Jency, Jaya Prabha, Technical Staffs Department of Medical Genetics, CMC Vellore Tamil Nadu. Ms Narayani, Scan Technician Department of Obstetrics and Gynecology CMC Vellore Tamil Nadu for their contribution.

Research ethics: IRB Min No: 14869 dated 28 Sep 2022, the Ethics Committee of the Christian Medical College and Hospital Vellore.
Informed consent: Informed and written consent was obtained from the patients prior to genetic testing.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: The authors state no conflict of interest.
Research funding: None declared.
Data availability: All data underlying the results are available as part of the article and no additional source data are required.

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Received: 2023-11-17

Accepted: 2024-03-04

Published Online: 2024-05-07

Published in Print: 2024-06-25

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Articles in the same Issue

https://doi.org/10.1515/jpm-2023-0485

Keywords for this article

syndrome; genetic counselling; consanguinity; congenital; proband