Focused Exome Sequencing Gives a High Diagnostic Yield in the Indian Subcontinent.
J Mol Diagn
; 26(6): 510-519, 2024 Jun.
Article
de En
| MEDLINE
| ID: mdl-38582400
ABSTRACT
The genetically isolated yet heterogeneous and highly consanguineous Indian population has shown a higher prevalence of rare genetic disorders. However, there is a significant socioeconomic burden for genetic testing to be accessible to the general population. In the current study, we analyzed next-generation sequencing data generated through focused exome sequencing from individuals with different phenotypic manifestations referred for genetic testing to achieve a molecular diagnosis. Pathogenic or likely pathogenic variants are reported in 280 of 833 cases with a diagnostic yield of 33.6%. Homozygous sequence and copy number variants were found as positive diagnostic findings in 131 cases (15.7%) because of the high consanguinity in the Indian population. No relevant findings related to reported phenotype were identified in 6.2% of the cases. Patients referred for testing due to metabolic disorder and neuromuscular disorder had higher diagnostic yields. Carrier testing of asymptomatic individuals with a family history of the disease, through focused exome sequencing, achieved positive diagnosis in 54 of 118 cases tested. Copy number variants were also found in trans with single-nucleotide variants and mitochondrial variants in a few of the cases. The diagnostic yield and the findings from this study signify that a focused exome test is a good lower-cost alternative for whole-exome and whole-genome sequencing and as a first-tier approach to genetic testing.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Dépistage génétique
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Variations de nombre de copies de segment d'ADN
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Limites:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Infant
/
Male
Pays/Région comme sujet:
Asia
Langue:
En
Journal:
J Mol Diagn
Sujet du journal:
BIOLOGIA MOLECULAR
Année:
2024
Type de document:
Article