Prevalence of mutations in inherited retinal diseases: A comparison between the United States and India

Sophia Yohe, Malaichamy Sivasankar, Anuprita Ghosh, Arkasubhra Ghosh, Jennifer Holle, Sakthivel Murugan, Ravi Gupta, Lisa A. Schimmenti, Ramprasad Vedam, Bharat Thyagarajan

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12 Scopus citations


Background: Studies evaluating next-generation sequencing (NGS) for retinal disorders may not reflect clinical practice. We report results of retrospective analysis of patients referred for clinical testing at two institutions (US and India). Methods: This retrospective study of 131 patients who underwent clinically validated targeted NGS or exome sequencing for a wide variety of clinical phenotypes categorized results into a definitive, indeterminate, or negative molecular diagnosis. Results: A definitive molecular diagnosis (52%) was more common in the India cohort (62% vs. 39%, p =.009), while an indeterminate molecular diagnosis occurred only in the US cohort (12%). In the US cohort, a lower diagnostic rate in Hispanic, non-Caucasians (23%) was seen compared to Caucasians (57%). The India cohort had a high rate of homozygous variants (61%) and different frequency of genes involved compared to the US cohort. Conclusion: Despite inherent limitations in clinical testing, the diagnostic rate across the two cohorts (52%) was similar to the 50%–65% diagnostic rate in the literature. However, the diagnostic rate was lower in the US cohort and appears partly explained by racial background. The high rate of consanguinity in the Indian population is reflected in the high rate of homozygosity for pathogenic mutations and may have implications for population level screening and genetic counseling. Clinical laboratories may note diagnostic rates that differ from the literature, due to factors such as heterogeneity in racial background or consanguinity rates in the populations being tested. This information may be useful for post-test counseling.

Original languageEnglish (US)
Article numbere1081
JournalMolecular Genetics and Genomic Medicine
Issue number2
StatePublished - Feb 1 2020

Bibliographical note

Publisher Copyright:
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.


  • clinical testing
  • molecular diagnosis
  • next-generation sequencing
  • racial disparity
  • retinal disorders


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