Journal
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
Volume 176, Issue 1, Pages 107-115Publisher
WILEY
DOI: 10.1002/ajmg.a.38542
Keywords
developmental delay; intellectual disability; re-evaluation; target sequencing; whole exome sequencing
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Funding
- Shanghai Municipal Commission of Health and Family Planning Foundation [201540054, 20154Y0153]
- National Natural Science Foundation of China [81400872, 30973216, 81401193]
- Shanghai Health Bureau [20134005]
- National Key Research and Development Program [2016YFC0905100]
- Shanghai Jiao Tong University School of Medicine [2014XJ10044]
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The diagnosis of intellectual disability/developmental delay (ID/DD) benefits from the clinical application of target/exome sequencing. The yield in Mendelian diseases varies from 25% to 68%. The aim of the present study was to identify the genetic causes of 33 ID/DD patients using target/exome sequencing. Recent studies have demonstrated that reanalyzing undiagnosed exomes could yield additional diagnosis. Therefore, in addition to the normal data analysis, in this study, re-evaluation was performed prior to manuscript preparation after updating OMIM annotations, calling copy number variations (CNVs) and reviewing the current literature. Molecular diagnosis was obtained for 19/33 patients in the first round of analysis. Notably, five patients were diagnosed during the re-evaluation of the geno/phenotypic data. This study confirmed the utility of exome sequencing in the diagnosis of ID/DD. Furthermore, re-evaluation leads to a 15% improvement in diagnostic yield. Thus, to maximize the diagnostic yield of next-generation sequencing (NGS), periodical re-evaluation of the geno/phenotypic data of undiagnosed individuals is recommended by updating the OMIM annotation, applying new algorithms, reviewing the literature, sharing pheno/genotypic data, and re-contacting patients.
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