|Title||Evaluating systematic reanalysis of clinical genomic data in rare disease from single center experience and literature review.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Tan, NB, Stapleton, R, Stark, Z, Delatycki, MB, Yeung, A, Hunter, MF, Amor, DJ, Brown, NJ, Stutterd, CA, McGillivray, G, Yap, P, Regan, M, Chong, B, Fernandez, MFanjul, Marum, J, Phelan, D, Pais, LS, White, SM, Lunke, S, Tan, TY|
|Journal||Mol Genet Genomic Med|
|Date Published||2020 11|
BACKGROUND: Our primary aim was to evaluate the systematic reanalysis of singleton exome sequencing (ES) data for unsolved cases referred for any indication. A secondary objective was to undertake a literature review of studies examining the reanalysis of genomic data from unsolved cases.
METHODS: We examined data from 58 unsolved cases referred between June 2016 and March 2017. First reanalysis at 4-13 months after the initial report considered genes newly associated with disease since the original analysis; second reanalysis at 9-18 months considered all disease-associated genes. At 25-34 months we reviewed all cases and the strategies which solved them.
RESULTS: Reanalysis of existing ES data alone at two timepoints did not yield new diagnoses. Over the same timeframe, 10 new diagnoses were obtained (17%) from additional strategies, such as microarray detection of copy number variation, repeat sequencing to improve coverage, and trio sequencing. Twenty-seven peer-reviewed articles were identified on the literature review, with a median new diagnosis rate via reanalysis of 15% and median reanalysis timeframe of 22 months.
CONCLUSION: Our findings suggest that an interval of greater than 18 months from the original report may be optimal for reanalysis. We also recommend a multi-faceted strategy for cases remaining unsolved after singleton ES.
|Alternate Journal||Mol Genet Genomic Med|
|PubMed Central ID||PMC7667328|
|Grant List||UM1 HG008900 / HG / NHGRI NIH HHS / United States|