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. 2024 May 7;52(5):520-529.
doi: 10.1515/jpm-2023-0485. Print 2024 Jun 25.

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  1 , Janane Elangovan  1   2 , Sumita Danda  1 , Manisha M Beck  3 , Preethi Navaneethan  3 , Rekha Athiyarath  1
Affiliations

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 et al. J Perinat Med. .

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

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