Parallel detection of single nucleotide variants and copy number variants with exome analysis: Validation in a cohort of 700 undiagnosed patients

Hisato Suzuki, Mamiko Yamada, Tomoko Uehara, Toshiki Takenouchi, Kenjiro Kosaki

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Copy number variants (CNVs) are significant causes of rare and undiagnosed diseases. Parallel detection of single nucleotide variants (SNVs) and CNVs with exome analysis, if feasible, would shorten the diagnostic closure in a timely manner. We validated such “parallel” approach through a cohort study of 791 undiagnosed patients. In addition to routine exome analysis, we applied an innovative algorithm EXCAVATOR2 which enhances sensitivity by paradoxically exploiting read depth data that covers nonexonic regions where baits were not originally intended to hybridize. About 48 patients had copy number variations, 42 deletions, and 6 duplications with a resolution of 0.51–14.7 mega base pairs. Importantly from a clinical standpoint, we identified three patients with “dual diagnosis” due to concurrent pathogenic CNV and SNV. We suggest “hitting two birds with one stone” approach to exome data is an efficient strategy in deciphering undiagnosed patients and may well be considered as a first-tier genetic test.

Original languageEnglish
Pages (from-to)2529-2532
Number of pages4
JournalAmerican Journal of Medical Genetics, Part A
Volume182
Issue number11
DOIs
Publication statusPublished - 2020 Nov 1

Keywords

  • chromosomal microarray
  • copy number variants
  • exome sequencing
  • undiagnosed diseases

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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